<PAGE>

                                                                  EXECUTION COPY
                                                                  April 19, 2000

                                                                   EXHIBIT 10.66



                         CONFIDENTIAL PORTIONS OMITTED
                         -----------------------------


                               OPTION AGREEMENT

                                    between

                         CORTEX PHARMACEUTICALS, INC.

                                      and

                               SHIRE HOLDINGS AG

                          dated as of April 19, 2000
<PAGE>

                               OPTION AGREEMENT

     THIS OPTION AGREEMENT (the "Agreement") dated as of April 19, 2000 (the
"Effective Date") is made between CORTEX PHARMACEUTICALS, INC., a Delaware
corporation having its principal offices at 15241 Barranca Parkway, Irvine,
California 92618 U.S.A. ("Cortex"), and SHIRE HOLDINGS AG having its principal
offices at Bundesstrasse 5, 6300 Zug, Switzerland ("Shire").

                                R E C I T A L S

     A.  Cortex possesses know-how, expertise and rights to issued United States
patents and patent applications and corresponding foreign filed patent
applications pertaining to a class of proprietary pharmaceuticals called
Ampakines(R).

     B.  Certain of these Ampakines(R), in particular "CX516", have the
potential to modulate and treat ADHD (as defined below).

     C.  Shire desires to investigate the potential usefulness of CX516 in the
treatment of ADHD during the Research Program under this Agreement, and at the
end of the Research Program, have the option to enter into an exclusive license
to use the Cortex Patent Rights and Cortex Technology to develop, manufacture
and commercialize a selected Ampakine(R) for the treatment of ADHD (the
"Option").

     NOW THEREFORE, in consideration of the premises and of the covenants herein
contained, the parties hereto mutually agree as follows:

                                1.  DEFINITIONS

     For purposes of this Agreement, the terms defined in this Article shall
have the meanings specified below:

1.1  "Affiliate" shall mean any corporation or other entity which controls, is
      ---------
controlled by, or is under common control with a Party to this Agreement.  A
corporation or other entity shall be regarded as in control of or controlled by
another corporation or entity if it owns or directly or indirectly controls more
than fifty percent (50%) of the voting stock or other ownership interest of the
other corporation or entity, or if it possesses, directly or indirectly, the
power to direct or cause the direction of the management and policies of the
corporation or other entity or the power to elect or appoint fifty percent (50%)
or more of the members of the governing body of the corporation or other entity.

1.2  "ADHD" shall mean Attention Deficit/Hyperactivity Disorders as defined in
      ----
the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition as
maybe amended from time to time.

1.3  "Ampakines(R)" shall mean those chemicals that are modulators of AMPA-
      ------------
receptor function and which are covered by the Cortex Patent Rights and/or
incorporate, use or were developed with the Cortex Technology.

1.4  "Assignment Fee" shall have the meaning set forth in Section 10.2.3.
      --------------

1.5  "Cortex Patent Rights" shall mean all rights useful in the Field under
      --------------------
present and future, foreign and domestic, patents, patent applications, patent
extensions, certificates of invention and

                                       1
<PAGE>

applications for certificates of invention, together with any originals,
provisionals, divisionals, continuations or continuations-in-part, extensions,
renewals and reissues owned by, or licensed to Cortex. Cortex Patent Rights as
of the Effective Date, and all licenses relating to such Cortex Patent Rights,
are listed in Schedule 1.5 hereto.
              ------------

1.6  "Cortex Technology" shall mean all present and future inventions, trade
      -----------------
secrets, copyrights, data, regulatory submissions or other intellectual property
of any kind useful in the Field (including any proprietary biological materials,
compounds or reagents) and all confidential technical information owned or
controlled by Cortex as of the Effective Date and during the term of this
Agreement necessary or useful for the discovery, development, manufacture, use
or sale of a Product and including Cortex Patent Rights, but excluding the Data.

1.7  "CX 516" shall mean 1-(Quinoxalin-6-ylcarbonyl) piperdine, the
      ------
specifications of which are attached hereto as Schedule 3.2.1.

1.8  "Data" shall have the meaning set forth in Section 2.5.
      ----

1.9  "Development and License Agreement" shall mean the agreement between the
      ---------------------------------
Parties for the exclusive worldwide license to manufacture, have manufactured,
use, supply, distribute and sell certain Ampakines(R) to be entered into on
exercise of the Option in the terms set out in the form attached hereto as
Exhibit A.
---------

1.10  "Effective Date" shall mean the date first set forth above.
       --------------

1.11 "Field" shall mean the use of Ampakines(R) for the treatment of ADHD.
      -----

1.12 "First Dosing" shall mean the first administration of a Product to a human
      ------------
subject in the Research Program as described in Section 2.1 below.

1.13 "IND" shall mean an Investigational New Drug application filed with the
      ---
Food and Drug Administration of the United States.

1.14 "Inventions," "Cortex Inventions" and "Shire Inventions" shall have the
      -----------   -----------------       ----------------
meanings set forth respectively in Section 6.1.1.

1.15 "Joint Inventions" shall have the meaning set forth in Section 6.1.1.
      ----------------

1.16 "Option" shall mean Shire's Option to license the Cortex Patent Rights and
      ------
Cortex Technology as set forth in Section 4.1.

1.17 "Option Period" shall have the meaning set forth in Section 4.2.
      -------------

1.18 "Party" shall mean Cortex or Shire.
      -----

1.19 "Product" shall mean any therapeutic composition for administration to
      -------
human subjects containing an Ampakine(R) as a pharmaceutically active
ingredient.

1.20 "Research License" shall have the meaning set forth in Section 3.1.
      ----------------

1.21 "Research Program" shall have the meaning set forth in Section 2.1.
      ----------------

                                       2
<PAGE>

1.22 "Selected Compounds" shall mean the two (2) AMPAKINES selected by Cortex
      ------------------
and provided to Shire for Shire for review and consideration pursuant to Section
2.1.2.

1.23 "Stock Purchase Agreement" shall mean the agreement between the Parties for
      ------------------------
Shire to invest in the Common Stock of Cortex on the terms set out in Exhibit B
                                                                      ---------
hereto.

1.24 "Third Party" shall mean any entity other than Cortex or Shire and their
      -----------
respective Affiliates.

1.25 "UCI License" shall mean the Exclusive License Agreement dated June 15,
      -----------
1993, between Cortex Pharmaceuticals, Inc. and The Regents of the University of
California.

                              2.  CLINICAL STUDY

2.1  Clinical Study and Information Analysis.

     2.1.1  CX516 Feasibility Study.  Within thirty (30) days after the
            -----------------------
  Effective Date, Cortex shall supply to Shire such information and materials in
  its possession or under its control relating to CX516 which is necessary or
  useful to enable Shire to procure an IND and conduct a suitable program to
  investigate the potential usefulness of CX516 in the Field (the "Research
  Program").  The Research Program shall pertain to CX516 only and not the
  Selected Compounds.  Subject to the grant of an IND, Shire shall, or cause its
  agents or contractors to, conduct the Research Program in a timely manner, in
  good scientific manner and in compliance with all applicable legal
  requirements, in accordance with Schedule 2.1.1 hereto.

     2.1.2  Additional Cortex Compounds.  Within six (6) months from the
            ---------------------------
  Effective Date, Cortex shall supply to Shire such information and materials in
  its possession or control relating to the Selected Compounds, as may be
  necessary or desirable in order for Shire to review and assess such compounds
  as potential candidates for development.  Shire shall be entitled to analyze
  the Selected Compounds for potential development as a Product.  Cortex shall
  chose the Selected Compounds based on the compound selection criteria referred
  to in Section 3.4 below.

2.2  Materials.  Cortex shall in a timely manner furnish Shire with sufficient
     ---------
quantities of CX516 pursuant to Section 3.2 below.

2.3  Regulatory Filings.  Shire, with the reasonable cooperation of Cortex,
     ------------------
shall endeavor to file an IND for the use of CX516 in the Field.  Except as set
forth in Sections 4.6 and 10.2 below, Shire shall own all rights under any IND
it files for CX516 pursuant to this Agreement.

2.4  Subcontracts.  Shire may subcontract all or portions of the Research
     ------------
Program to Third Parties without the prior consent of Cortex; provided, however,
that Shire shall require such Third Parties to enter into appropriate
confidentiality agreements unless such subcontracting would not require the
transfer of confidential Information (as defined in Article 7 hereof) to the
Third Party.

2.5  Data.  Shire shall use its reasonable efforts to cause Third Parties
     ----
conducting the Research Program to maintain records in sufficient detail as such
will properly reflect all work done and results achieved in the performance of
the Research Program (including all data in the form required to be maintained
under any applicable governmental regulations) and maintain such records in good
scientific manner and in compliance with applicable laws and regulations.  Such
records shall comprise books, results, reports, research notes, charts, graphs,
comments, computations, analyses, recordings, photographs, computer programs and
documentation thereof, computer information

                                       3
<PAGE>

storage means, samples of materials, regulatory submissions, including the IND
and other graphic or written data generated in connection with the Research
Program (the "Data"). Shire shall, on Cortex's reasonable request, provide to
Cortex summaries of the Data provided, however, that Cortex shall maintain such
records and the information of Shire contained therein in confidence in
accordance with Article 7 below and shall not use such records or information of
Shire except to the extent otherwise permitted by this Agreement. Shire shall
own all intellectual property rights pertaining to the Data and, except as
otherwise expressly provided in this Agreement, Cortex shall have no right of
use or ownership of the Data.

2.6  Communication.  Shire shall keep Cortex reasonably informed of its progress
     -------------
under the Research Program as necessary.

2.7  Adverse Event Reports.  Each Party shall promptly report to the other
     ---------------------
potentially serious or unexpected adverse events (including adverse drug
experiences, as defined in 21 C.F.R. (S) 314.80 or other applicable regulations)
with respect to Ampakines(R) of which it becomes aware and in no event later
than five (5) days after initial receipt of the information by such party with
the exception of Life-Threatening Adverse Drug Experiences (as defined in 21
C.F.R. (S) 314.80(a)), which shall be notified to the other party within 24
hours of receipt of knowledge by the notifying party.  Each Party shall report
to the other Party summaries of other adverse events with respect to every
twelve (12) months.  Cortex may provide such information that it receives from
Shire under this Section 2.7 to its other licensees.  Cortex shall use
commercially reasonable efforts to include in its other agreements, similar
provisions to this Section 2.7.

2.8  Availability of Employees.  Each Party agrees to make its employees and
     -------------------------
nonemployee consultants reasonably available at their respective places of
employment to consult with the other Party on issues arising during the Research
Program and in connection with any request from any regulatory agency, including
regulatory, scientific, technical and clinical testing issues.

2.9  Visit of Facilities.  Representatives of each Party may, upon reasonable
     -------------------
notice and at times reasonably acceptable to the other Party, visit the other
Party's facilities or clinics where the Research Program is being conducted, and
consult informally, during such visits and by telephone, with the other Party's
personnel performing in the Research Program.  Such representative shall abide
by all operating procedures and rules of the facilities or clinics with respect
to safety and confidentiality and the relevant Party shall be liable for the
actions of its representatives during any such facility visit.

                          3.  LICENSES; MANUFACTURING

3.1  Grant of Research License.  Cortex hereby grants to Shire the worldwide
     -------------------------
exclusive right and license, with the right to sublicense, in the Field under
the Cortex Patent Rights, Cortex Technology, Cortex Inventions and Cortex's
interest in Joint Inventions to the extent necessary or useful to carry out
Shire's research and development responsibilities on CX516 and the Selected
Compounds during the Research Program in accordance with this Agreement (the
"Research License").

     3.1.1  UCI License.  Upon the execution and delivery by Cortex of this
            -----------
  Agreement to Shire, Cortex shall deliver to Shire a letter from The Regents of
  the University of California (the "Regents"), which shall state (i) Cortex is
  not currently in default of the UCI License and (ii) if the UCI License is
  terminated for any reason by the Regents, then the Regents shall grant the
  Regents' Patent Rights (as defined in the UCI License) directly to Shire on
  substantially the same

                                       4
<PAGE>

  terms and conditions as the same Regents' Patents Rights were granted to
  Cortex under the UCI License. If the UCI License is terminated for any reason
  by the Regents, then Cortex shall, upon such termination, use commercially
  reasonable efforts to obtain the direct license between the Regents and Shire
  for the Regents' Patent Rights, as contemplated in the immediately preceding
  sentence.

3.2  Manufacture of CX516.
     --------------------

     3.2.1.  Supply.  Cortex shall be responsible for the supply of CX516 at the
             ------
  required quality and in quantities sufficient to conduct the Research Program
  and in compliance with the ingredient specifications attached hereto as
  Schedule 3.2.1.  Cortex shall manufacture, or cause to be manufactured, CX516
  --------------
  supplied hereunder in accordance with current Good Manufacturing Practices
  promulgated by the U.S. Food and Drug Administration.  Cortex shall at its own
  expense deliver supplies of CX 516 to such premises in the U.S. as shall be
  notified in advance to it by Shire and risk shall transfer to Shire upon
  delivery.

     3.2.2  Purchase by Shire.  Shire shall purchase the first five (5)
            -----------------
  kilograms of CX 516 it requires at [*] per kilogram.  Thereafter, CX 516
  supplies shall be provided at the actual documented cost to Cortex.

3.3  Reservation of Rights.  Cortex at all times reserves the right under the
     ---------------------
Cortex Patent Rights, Cortex Technology, Cortex Inventions and Cortex's interest
in Joint Inventions to make and use CX516 and the Selected Compounds for its own
research purposes outside the Field.

3.4  Compound Selection Criteria.  Within six (6) months of the Effective Date,
     ---------------------------
Cortex shall provide to Shire a description of the criteria it has used in
selecting the Selected Compounds and will use in selecting additional
Ampakines(R) pursuant to Section 3.4.1 of the License Agreement, which criteria
shall be compiled with reasonable care and skill and shall be objective grounds
for selecting criteria Ampakines(R) which are the most promising candidates in
terms of safety, efficacy and commercial viability with potential for usefulness
in the Field.

                                  4.  OPTION

4.1  Grant of Option.  Cortex hereby grants to Shire an exclusive option (the
     ---------------
"Option") to enter into the Development and License Agreement, subject to the
terms and conditions of this Article 4.

4.2  Option Period.  The Option granted in Section 4.1 shall be for the term of
     -------------
[*].  The Option will commence on the earlier of the date of [*] after the
Effective Date, unless otherwise extended by mutual written consent by the
Parties (the "Option Period").  Cortex shall not unreasonably withhold its
consent to extend the Option Period to a period ending two (2) months from
completion of the Research Program in circumstances where completion of the
Research Program is delayed due to factors outside of the reasonable control of
Shire, including but not limited to Cortex's failure to carry out any obligation
under this Agreement.  In no event shall the Option Period expire later than [*]
from the Effective Date.

* CONFIDENTIAL PROVISIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION

                                       5
<PAGE>

4.3  Exclusivity of Option Period.  Except for the Research License granted in
     ----------------------------
Section 3.1 above, Cortex shall retain all right, title and interest in and to
CX516, the Cortex Patent Rights, the Cortex Technology, the Cortex Inventions
and Cortex's interest in Joint Inventions.  From the Effective Date through the
end of the Option Period, Cortex shall not license, sell, transfer or in any
manner encumber (i) the Cortex Patent Rights, Cortex Technology the Cortex
Inventions and Cortex's Interest in Joint Inventions inside the Field or (ii)
CX516 and the Selected Compounds inside or outside the Field.

4.4  Expiration or Termination of Option.  If Shire does not exercise the Option
     -----------------------------------
hereunder prior to the expiration of the Option Period, or if prior to the
expiration of the Option Period, Shire shall advise  Cortex that it does not
desire to exercise the Option, neither Party shall thereafter be under any
further obligation under this Agreement (except that the applicable terms of
Section 10.2 shall apply), and at such time as the Option Period expires or when
Shire has provided Cortex with written notice of non-election of the Option,
Cortex shall be free to license the Cortex Patent Rights, Cortex Technology the
Cortex Inventions and Cortex's interest in Joint Inventions to Third Parties
inside or outside the Field, without any obligation to Shire whatsoever and any
Research License granted to Shire under Section 3.1 shall immediately terminate.

4.5  Exercise of Option.
     ------------------

     4.5.1  Option Notice.  In order to assist Shire in determining whether to
            -------------
  exercise the Option pursuant to Section 4.5.2 below, Cortex shall within
  fourteen (14) days of receipt of a written request from Shire: (i) identify
  all AMPAKINES then available for continued investigation and possible
  development pursuant to the Development and License Agreement and (ii) provide
  to Shire the research plan for conducting on Ampakines(R), which will be
  attached as Schedule 1.35 to the Development and License Agreement pending
              -------------
  final approval by Shire.

     4.5.2  Exercise of Option.  Should Shire decide to exercise the Option, it
            ------------------
  shall do so by so notifying Cortex in writing at any time during the Option
  Period.  Upon such notification by Shire, the Parties promptly shall execute
  and deliver the Development and License Agreement, in the form attached hereto
  as Exhibit A.
     ---------

4.6  Transfer of Ownership of IND.  If Shire has filed an IND for CX516 in the
     ----------------------------
Field as set forth above in Section 2.3, and the Option lapses or is terminated
pursuant to Section 4.4 above or Cortex terminates the Agreement pursuant to
Section 10.1 below, then, upon the payment of the Assignment Fee by Cortex the
ownership of the Data shall transfer to Cortex and Cortex shall solely own all
rights to such data, including any Data filed by Shire for CX516 in the Field.
If ownership to the Data should transfer to Cortex pursuant to this Section 4.6,
Shire agrees execute and deliver such instruments and take such other actions as
Cortex shall reasonably request in order to carry out the transfer of the Data
from Shire to Cortex, including but not limited to, transfer of regulatory
approvals.

                                 5.  PAYMENTS

5.1  Funding of the Research Program.  Except as otherwise provided in this
     -------------------------------
Agreement or agreed by the Parties, Shire shall bear all of the costs incurred
in connection with the Research Program.

5.2  Consideration.  Upon the execution of this Agreement, Shire shall pay to
     -------------
Cortex an option fee of One Hundred and Thirty Thousand Dollars ($130,000) by
wire transfer to an account

                                       6
<PAGE>

designated by Cortex and the parties shall enter into the Stock Purchase
Agreement in the form attached hereto as Exhibit B.
                                         ---------

                       6.  INTELLECTUAL PROPERTY RIGHTS

6.1  Ownership.
     ---------

     6.1.1  Ownership of Inventions.  Inventorship with respect to inventions
            -----------------------
  made pursuant to work carried out during the Investigation Phase shall be
  determined in accordance with United States rules of inventorship.  All right,
  title and interest in all writings, inventions, discoveries, improvements and
  other technology whether or not patentable or copyrightable, and any patent
  applications, patents or copyrights based thereon and which relate to the
  Ampakines(R) (collectively, the "Inventions") that are conceived and/or
  reduced to practice during and as a result of the Research Program solely by
  employees of Cortex or others acting on behalf of Cortex ("Cortex Inventions")
  shall be owned by Cortex.  All right, title and interest in all Inventions
  that are conceived and/or reduced to practice during and as a result of the
  Research Program solely by employees of Shire or others acting on behalf of
  Shire ("Shire Inventions") shall be owned by Shire.  All right, title and
  interest in all Inventions that are conceived and/or reduced to practice
  during and as a result of the Research Program jointly by employees of Cortex
  and Shire (the "Joint Inventions") shall be owned jointly by Shire and Cortex.
  The responsibilities and rights with respect to such Inventions shall be as
  set forth in Section 9 of the Development and License Agreement whether or not
  the Development and License Agreement is entered into by the Parties pursuant
  to Section 4.5.

     6.1.2  Cooperation of Employees.  Each Party represents and agrees that all
            ------------------------
  employees or others acting on its behalf in performing its obligations under
  this Agreement shall be obligated under a binding written agreement to assign
  to such Party, or as such Party shall direct, all Inventions made or conceived
  by such employee or other person, or in the case of non-employees working for
  other companies or institutions on behalf of Cortex or Shire, except where
  such assignment is required by law.

                              7.  CONFIDENTIALITY

7.1  Nondisclosure Obligations.  Except as otherwise provided in this Article 7,
     -------------------------
during the term of this Agreement and for a period of ten (10) years thereafter,
both Parties shall maintain in confidence and use only for purposes specifically
authorized under this Agreement information and data received from the other
Party in connection with this Agreement and the Research Program
("Information").

     To the extent it is reasonably necessary or appropriate to fulfil its
obligations or exercise its rights under this Agreement, a Party may disclose
Information it is otherwise obligated under this Section not to disclose to its
Affiliates, sublicensees, consultants, professional advisors, outside
contractors and clinical investigators, on a need-to-know basis on condition
that such entities or persons agree to confidentiality and non-use provisions in
relation to the Information on such terms as the disclosing Party uses for its
own confidential information of similar commercial importance, and a Party, its
Affiliate or its sublicensees or contractors may disclose such Information to
government or other regulatory authorities to the extent that such disclosure is
reasonably necessary to obtain patents or authorizations to conduct clinical
trials, is required by law or regulation.  The obligation not to disclose
Information shall not apply to any part of such Information that (i) is or

                                       7
<PAGE>

becomes patented or published (ii) is or becomes part of the public domain other
than by acts of the Party obligated not to disclose such Information or its
Affiliates or sublicensees in contravention of this Agreement; (iii) is
disclosed to the receiving Party or its Affiliates or sublicensees by a Third
Party, provided such Information was not knowingly obtained by such Third Party
directly or indirectly from the other Party under this Agreement; (iv) prior to
disclosure under this Agreement, was already in the possession of the receiving
Party or its Affiliates or sublicensees, provided such Information was not
knowingly obtained directly or indirectly from the other Party under this
Agreement; or (v) can be shown by written documents to have been independently
developed by the receiving Party or its Affiliates or sublicensees without aid
of or reference to the Information.

7.2  Terms of this Agreement.  Cortex and Shire each agrees not to disclose any
     -----------------------
terms or conditions of this Agreement to any Third Party without the prior
consent of the other Party, except as required by applicable law or to persons
with whom Shire or Cortex has entered into or proposes to enter into a business
relationship provided that such persons are subject to appropriate
confidentiality agreements.  If a Party is required by law or regulation to
disclose Information to its government or other regulatory authorities, that
Party shall make reasonable efforts to keep the Information confidential and
protected from public disclosure.

7.3  Publications.  In the event that either Party wishes to make a publication
     ------------
(which term shall include any oral disclosure to be made without obligation of
confidentiality) relating to any results obtained pursuant to or in connection
with this Agreement (the "Publishing Party"), it shall submit to the other Party
a copy of the proposed publication at least forty-five (45) days prior to the
intended date of submission for publication (or, in the case of an oral
disclosure, a written abstract thereof at least fifteen (15) days prior to the
date of intended disclosure); and

     7.3.1  subject to Section 7.3.2 below, if the Publishing Party is Cortex,
  Shire shall have the right to delay or prevent publication as it sees fit; or

     7.3.2  if the Publishing Party is Shire, or is Cortex (but only where
  Cortex is subject to a Third Party obligation to seek to publish, evidence of
  which shall be provided on Shire's request), the other Party shall be entitled
  to propose modifications or request a delay in publication of up to forty-five
  (45) days in order to obtain relevant patent protection.  Following
  consideration of the other Party's comments or expiry of the forty-five (45)
  day period (as appropriate), the Publishing Party shall be free to publish.

7.4  Press Release.  The Parties shall agree the content of the press release to
     -------------
be issued on execution of this Agreement, annexed hereto as Exhibit C.  In
                                                            ---------
relation to subsequent press releases, Shire shall submit a draft to Cortex in
sufficient time to enable Cortex to consider and comment thereon and the Parties
shall co-operate in good faith as to the form, content and timing of any
announcement.  Neither Party shall make any public announcement relating to the
terms of this Agreement, its subject matter or performance under it, to the
extent not previously publicly disclosed, without the prior written consent of
the other Party (which shall not be unreasonably withheld or delayed) except
such as may be required by law or the rules any stock exchange, in which case
the other Party will be given as much notice as is reasonably practicable in
order to allow such Party to comment thereon.

                                       8
<PAGE>

                      8.  REPRESENTATIONS AND WARRANTIES

8.1  Authorization.  Each Party represents and warrants to the other that it has
     -------------
the legal right and power to enter into this Agreement, to extend the rights and
licenses granted or to be granted to the other in this Agreement, and to fully
perform its obligations hereunder, and that it has not made nor will it make any
commitments to others in conflict with or in derogation of such rights or this
Agreement.  Except as otherwise disclosed, each Party further represents to the
other that it is not aware of any legal obstacles, including, patent rights of
others, which could prevent it from carrying out its obligations under this
Agreement.

8.2  Intellectual Property Representations and Warranties.
     ----------------------------------------------------

     8.2.1  Patent Rights.  Except as otherwise set forth in Schedule 1.5,
            -------------                                    ------------
  Cortex represents and warrants that it is the sole and exclusive owner or
  exclusive licensee of the entire right, title and interest in and to the
  Cortex Patent Rights, as set forth in Schedule 1.5 hereto, and the Cortex
                                        ------------
  Technology and that it has the right to license the same to Shire under this
  Agreement.  Cortex represents and warrants that, as of the Effective Date the
  Cortex Patent Rights and the Cortex Technology are free of any encumbrances,
  including, without limitation, liens, licenses, judgments and/or security
  interests in the Field, and that all patents and patent applications included
  in the Cortex Patent Rights are in full force and effect as of the date hereof
  of this Agreement and that none of the Cortex Patent Rights are the current
  subject of any interference or opposition proceeding.

     8.2.2  Litigation.  Cortex represents and warrants that as of the Effective
            ----------
  Date there is no pending, or to its knowledge threatened, litigation that
  would or might adversely affect its right and ability to grant the licenses
  and to perform its obligations under this Agreement.

     8.2.3  Validity and Infringement.  Cortex makes no representation or
            -------------------------
  warranty as to the validity of any of its patents and applications which are
  included in the Cortex Patent Rights, or as to the non-infringement of any
  Third Party patent(s) by the manufacture, use or sale of compounds or products
  or the practice of any processes or methods covered by the Cortex Patent
  Rights by Cortex, its Affiliates or licensees.  However, Cortex does represent
  and warrant that to the best of its knowledge, as of the date hereof:  (i) it
  is unaware of any publications or activities--including, without limitation,
  patents, articles, and public uses or sales, by it or others, which would or
  might invalidate any claim(s) of any patent or patent application included in
  the Cortex Patent Rights, (ii) it has not conducted or had reported to it, or
  has not commissioned the conducting of, any formal or informal infringement or
  validity studies regarding any patent or patent application included in the
  Cortex Patent Rights that it has not fully disclosed in writing to Shire prior
  to the date hereof; (iii) it has disclosed to Shire any Third Party patent(s)
  of which it is aware that might be infringed by the manufacture, use or sale
  of any compounds or products or the practice of any methods or processes
  covered by the Cortex Patent Rights by Shire, its Affiliates or sublicensees,
  (iv) it is not aware of any claim or accusation whether outstanding or
  resolved that any compounds or products manufactured, used or sold by Cortex
  or any methods or process practiced by Cortex which are included in the rights
  granted to Shire in this Agreement or will be used by Cortex on carrying out
  its obligations under this Agreement infringes or may infringe any Third Party
  patent(s) or other right, and (v) it does not own or license any patents or
  patent applications not included in the Cortex Patent Rights which would be
  infringed by the

                                       9
<PAGE>

  manufacture, use or sale of any compounds or products or the practice of any
  methods or processes covered by the Cortex Patent Rights or included in the
  Cortex Technology by Shire, its Affiliates or sublicensees.

     8.2.4  Maintenance of Confidential Information.  Cortex represents and
            ---------------------------------------
  warrants that it has taken all reasonable and necessary steps to protect the
  Cortex confidential Information contained in the Cortex Patents and Cortex
  Technology.

                          9.  INDEMNITY AND INSURANCE

 9.1 Indemnification.
     ---------------

     9.1.1  Cortex Indemnity Obligations.  Cortex agrees to defend, indemnify
            ----------------------------
  and hold Shire, its Affiliates and their respective employees and agents
  harmless from all Third Party claims, losses, damages or expenses, but
  excluding consequential losses, including, without limitation, economic loss
  or loss of profit, arising as a result of: (a) the negligent, willful or
  tortious acts or omissions of Cortex, its Affiliates and their respective
  employees and agents; or (b) any breach of Cortex's representations and
  warranties herein.

     9.1.2  Shire Indemnity Obligations.  Shire agrees to defend, indemnify and
            ---------------------------
  hold Cortex, its Affiliates and their respective employees and agents harmless
  from all Third Party claims, losses, damages or expenses, but excluding
  consequential losses, including, without limitation, economic loss or loss of
  profit, arising as a result of: (a) the negligent, willful or tortious acts or
  omissions of Shire, its Affiliates and their respective employees and agents;
  or (b) any breach of Shire's representations and warranties herein.

     9.1.3  Procedure.  A Party or any of its Affiliates or their respective
            ---------
  employees or agents (the "Indemnitee") that intends to claim indemnification
  under this Article 9 shall promptly notify the other Party (the "Indemnitor")
  of any loss, claim, damage, liability or action in respect of which the
  Indemnitee intends to claim such indemnification, and the Indemnitor shall
  assume the defense thereof with counsel mutually satisfactory to the Parties;
  provided, however, that an Indemnitee shall have the right to retain its own
  counsel, with the fees and expenses to be paid by the Indemnitor, if
  representation of such Indemnitee by the counsel retained by the Indemnitor
  would be inappropriate due to actual or potential conflicting interests
  between such Indemnitee and any other Party represented by such counsel in
  such proceedings.  The indemnity agreement in this Article 9 shall not apply
  to amounts paid in settlement of any loss, claim, damage, liability or action
  if such settlement is effected without the consent of the Indemnitor, which
  consent shall not be withheld unreasonably.  The failure to deliver notice to
  the Indemnitor within a reasonable time after the commencement of any such
  action, if materially prejudicial to its ability to defend such action, shall
  relieve such Indemnitor of any liability to the Indemnitee under this Article
  9, but the omission so to deliver notice to the Indemnitor will not relieve it
  of any liability that it may have to any Indemnitee otherwise than under this
  Article 9.  The Indemnitee under this Article 9, its employees and agents,
  shall cooperate fully with the Indemnitor and its legal representatives in the
  investigation of any action, claim or liability covered by this
  indemnification.  In the event that either Party claims indemnity from the
  other and one Party is finally held liable to indemnify the other, the
  Indemnitor shall additionally be liable to pay the reasonable legal costs and
  attorneys' fees incurred by the Indemnitee in establishing its claim for
  indemnity.

                                      10
<PAGE>

9.2  Insurance.
     ---------

     9.2.1  Shire Insurance Obligations.  Shire shall maintain comprehensive
            ---------------------------
  general liability insurance against claims regarding the implementation and
  execution of the Research Program, in such amounts as Shire customarily
  maintains with similar activities.  Shire shall maintain such insurance during
  the term of this Agreement and thereafter for so long as it customarily
  maintains insurance for itself  for similar activities.  Shire shall provide
  Cortex proof of such insurance upon request.  Shire shall give Cortex at least
  thirty (30) days notice of any cancellation, termination or change in such
  insurance

     9.2.2  Cortex Insurance Obligations.  Cortex shall maintain comprehensive
            ----------------------------
  general liability insurance, including product liability insurance against
  claims regarding the supply of the Products under this Agreement, in such
  amounts as it customarily maintains for similar products and activities.
  Cortex shall maintain such insurance during the term of this Agreement and
  thereafter for so long as it customarily maintains insurance for itself for
  similar products and activities.  Cortex shall provide Shire proof of such
  insurance upon request.  Cortex shall give Shire at least thirty (30) days
  notice of any cancellation, termination or change in such insurance.

                           10.  TERM AND TERMINATION

10.1 Termination of This Agreement.  This Agreement may be terminated in the
     -----------------------------
following circumstances:

     10.1.1  Material Breach.  By one Party upon written notice by reason of a
             ---------------
  material breach by the other Party that (if capable of remedy) the breaching
  Party fails to remedy within ninety (90) days after written notice thereof by
  the non-breaching Party, or in the case that such breach cannot be cured
  within such period, the breaching Party continues to use diligent efforts to
  cure such breach until actually cured;

     10.1.2  Bankruptcy.  By either Party upon bankruptcy, insolvency,
             ----------
  dissolution or winding up of the other.

     10.1.3  Failure to Exercise Option.  By Cortex, if Shire has failed to
             --------------------------
  exercise the Option within the Option Period pursuant to Section 4.2.

     10.1.4  Upon Exercise of Option. Upon exercise of the Option, the
             -----------------------
Development and License Agreement shall be immediately effective and this
Agreement shall terminate immediately.  For record keeping purposes, Parties
shall endeavor to promptly execute the Development and License Agreement,
provided however that failure of either Party to so execute shall not invalidate
or terminate the Development and License Agreement.

     10.1.5  [*]

10.2 Effect of Expiration or Termination.
     -----------------------------------

     10.2.1  Existing Obligations.  Expiration or termination of this Agreement
             --------------------
  for any reason shall not relieve the Parties of any obligation that accrued
  prior to such expiration or termination.

* CONFIDENTIAL PROVISIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION

                                      11
<PAGE>

     10.2.2  Survival.  The provisions of Articles 2.5, 6, 7, 9 and 10.2 shall
             --------
  survive the expiration or termination of this Agreement in accordance with
  their respective terms.

     10.2.3  Assignment of Data and Rights.  Upon expiration or termination of
             -----------------------------
  this Agreement, Shire shall, (a) deliver to Cortex any and all Data not
  previously delivered by Shire to Cortex for the payment by Cortex to Shire of
  [*] (the "Assignment Fee") and (b) to the extent legally permissible and at
  Cortex's expense, take all additional action reasonably requested by Cortex to
  assign all of its right, title and interest in and transfer possession and
  control to Cortex of all Data.

     10.2.4  Reversion of Ownership of Data and IND.  Upon the payment of the
             --------------------------------------
  Assignment Fee, the ownership of the Data, including any IND filed by Shire
  for CX516 for the Field will transfer to Cortex as set forth above in Section
  4.6.

     10.2.5  Wind-up Costs.  Shire will pay all costs, fees or expenses
             -------------
  associated with the termination of any clinical trial investigating CX516 as
  part of the Research Program upon termination of the Agreement by either Party
  pursuant to Section 10.1.

     10.2.6  Assignment of Shire Rights.  Upon expiration or termination of this
             --------------------------
  Agreement pursuant to Section 10.1, the Research License granted in Section
  3.1 shall terminate and all right and license in the Field under the Cortex
  Patent Rights, Cortex Technology, Cortex Inventions and Cortex's interest in
  Joint Inventions shall revert back to Cortex and Cortex will be the sole owner
  thereof.   If such rights and license should revert back to Cortex pursuant to
  this Section 10.2.6, Shire agrees, at Cortex's expense, execute and deliver
  such instruments and take such other actions as Cortex shall reasonably
  request in order to carry out the transfer of the Cortex Patent Rights, Cortex
  Technology, Cortex Inventions and Cortex's interest in Joint Inventions, from
  Shire to Cortex, including but not limited to patent assignments, and the
  assignment of regulatory approvals.

10.3 Additional Rights to Shire in the Event of Cortex Bankruptcy.  All licenses
     ------------------------------------------------------------
granted under this Agreement are deemed to be, for purposes of Section 365(n) of
the U.S. Bankruptcy Code, licenses of right to "intellectual property" as
defined in Section 101 of such Code.  The Parties agree that Shire may fully
exercise all of its rights and elections under the Bankruptcy Code.  The Parties
further agree that, in the event Shire elects to retain its rights as a licensee
under such Code, Shire shall be entitled to complete access to the Cortex
Technology and Patents licensed to it hereunder and all embodiments of such
Cortex Technology and Patents, for the purposes of exploitation of the licenses
granted under this Agreement.  Such embodiments of the Cortex Technology and
Patents shall be delivered to Shire not later than:

          (a) the commencement of bankruptcy proceedings against Cortex, upon
written request, unless Cortex elects to perform its obligations under the
Agreement, or

          (b) if not delivered under (a) above, upon the rejection of this
Agreement by or on behalf of the Cortex, upon written request.


* CONFIDENTIAL PROVISIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION

                                      12
<PAGE>

                              11.  MISCELLANEOUS

11.1 Force Majeure.  Neither Party shall be held liable or responsible to the
     --------------
other Party nor be deemed to have defaulted under or breached this Agreement for
failure or delay in fulfilling or performing any term of this Agreement when
such failure or delay is caused by or results from causes beyond the reasonable
control of the affected Party, including but not limited to fire, floods,
embargoes, war, acts of war (whether war is declared or not), insurrections,
riots, civil commotions, strikes, lockouts or other labor disturbances, acts of
God or acts, omissions or delays in acting by any governmental authority or the
other Party; provided, however, that the Party so affected shall use reasonable
commercial efforts to avoid or remove such causes of nonperformance, and shall
continue to perform hereunder with reasonable dispatch whenever such causes are
removed.  Either Party shall provide the other Party with prompt written notice
of any delay or failure to perform that occurs by reason of force majeure.  The
Parties shall mutually seek a resolution of the delay or the failure to perform
as noted above.

11.2 Assignment.  This Agreement may not be assigned or otherwise transferred by
     -----------
either Party without the prior written consent of the other Party, which consent
shall not be unreasonably withheld or delayed; provided, however, that each of
the Parties may, without such consent, assign this Agreement and its rights and
obligations hereunder to its Affiliates or in connection with the transfer or
sale of all or substantially all of its business, or in the event of its merger
or consolidation or change in control or similar transaction (which shall be
deemed an assignment).  Any purported assignment in violation of the preceding
sentences shall be void.  Any permitted assignee shall assume all obligations of
its assignor under this Agreement in writing.

11.3 Severability.  Each Party hereby agrees that it does not intend to violate
     ------------
any public policy, statutory or common laws, rules, regulations, treaty or
decision of any government agency or executive body thereof of any country or
community or association of countries.  Should one or more provisions of this
Agreement be or become invalid, the Parties hereto shall substitute, by mutual
consent, valid provisions for such invalid provisions which valid provisions in
their economic effect are sufficiently similar to the invalid provisions that it
can be reasonably assumed that the Parties would have entered into this
Agreement with such valid provisions.  In case such valid provisions cannot be
agreed upon, the invalidity of one or several provisions of this Agreement shall
not affect the validity of this Agreement as a whole, unless the invalid
provisions are of such essential importance to this Agreement that it is to be
reasonably assumed that the Parties would not have entered into this Agreement
without the invalid provisions.

11.4 Notices.  Any consent, notice or report required or permitted to be given
     -------
or made under this Agreement by one of the Parties hereto to the other shall be
in writing, delivered personally or by facsimile (and promptly confirmed by
personal delivery or courier) or courier, postage prepaid (where applicable),
addressed to such other Party at its address indicated below, or to such other
address as the addressee shall have last furnished in writing to the addressor
and shall be effective upon receipt by the addressee.

                                      13
<PAGE>

     If to Cortex:       Cortex Pharmaceuticals, Inc.
                         15241 Barranca Parkway
                         Irvine, California 92618
                         Attention:  Chief Executive Officer
                         Fax:  949/727-3657

     with a copy to:     Stradling Yocca Carlson & Rauth
                         660 Newport Center Drive, Suite 1600
                         Newport Beach, California 92660
                         Attention:  Lawrence B. Cohn
                         Fax:  949/725-4100

     If to Shire:        Shire Holdings AG
                         Bundesstrasse 5, 6300 Switzerland
                         Attention:  Company Secretary

     with a copy to:     Shire Pharmaceuticals Group
                         East Anton, Andover, Hampshire, SP10 5RG England
                         Attention:  Company Secretary
                         Fax:  (011) 44-1264-332-879

11.5 Governing Law, Venue.  This Agreement shall be governed by, and construed
     --------------------
in accordance with, the laws of the State of California and the United States,
as though made and to be fully performed therein without regard to conflicts of
laws principles thereof.  Except as set forth in Section 11.6 below, all
disputes with respect to this Agreement and the subject matter hereof shall be
heard exclusively in the state or federal courts in Orange County, California,
and the parties agree to the jurisdiction of such courts.

11.6 Arbitration.  Any disputes arising between the Parties relating to, arising
     -----------
out of or in any way connected with this Agreement or any term or condition
hereof, or the performance by either Party of its obligations hereunder, whether
before or after termination of this Agreement, shall be promptly presented to
the Chief Executive Officers of Cortex and Shire for resolution and if the Chief
Executive Officers cannot promptly resolve such disputes, then such dispute
shall be finally resolved by binding arbitration.  Whenever a Party shall decide
to institute arbitration proceedings, it shall give written notice to that
effect to the other Party.  The Party giving such notice shall refrain from
instituting the arbitration proceedings for a period of sixty (60) days
following such notice.  Any arbitration hereunder shall be conducted under the
Commercial Arbitration Rules of the American Arbitration Association.  Each such
arbitration shall be conducted by a panel of one or three arbitrators appointed
in accordance with such Rules.  Any such arbitration shall be held in Orange
County, California.  The arbitrators shall have the authority to grant specific
performance, and to allocate between the Parties the costs of arbitration in
such equitable manner as they determine.  Judgment upon the award so rendered
may be entered in any court having jurisdiction or application may be made to
such court for judicial acceptance of any award and an order of enforcement, as
the case may be.

11.7 Entire Agreement.  This Agreement, together with the Exhibits hereto and
     ----------------
the Stock Purchase Agreement between the Parties, dated the date hereof,
contains the entire understanding of the Parties with respect to the subject
matter hereof.  In the event of any conflict or inconsistency between any

                                      14
<PAGE>

provision of any Exhibit hereto and any provision of this Agreement, the
provisions of this Agreement shall prevail. All express or implied agreements
and understandings, either oral or written, heretofore made are expressly merged
in and made a part of this Agreement. This Agreement may be amended, or any term
hereof modified, only by a written instrument duly executed by both Parties
hereto.

11.8  Headings.  The captions to the several Articles and Sections hereof and
      --------
Exhibits hereto are not a part of this Agreement, but are merely guides or
labels to assist in locating and reading the several Articles and Sections
hereof.

11.9  Independent Contractors.  It is expressly agreed that Cortex and Shire
      -----------------------
shall be independent contractors and that the relationship between the two
Parties shall not constitute a partnership, joint venture or agency. Neither
Cortex nor Shire shall have the authority to make any statements,
representations or commitments of any kind, or to take any action, which shall
be binding on the other, without the prior consent of the other Party to do so.

11.10 Agreement Not to Solicit Employees.  During the term of this Agreement
      ----------------------------------
and for a period of either:  (i) one (1) year from the expiration or termination
of the Option, or (ii) two (2) years following the termination of this Agreement
upon Shire's exercise of the Option, Cortex and Shire agree not to seek to
persuade or induce any employee of the other company to discontinue his or her
employment with that company in order to become employed by or associated with
any business, enterprise or effort that is associated with its own business.

11.11 Waiver.  The waiver by either Party hereto of any right hereunder or the
      ------
failure to perform or of a breach by the other Party shall not be deemed a
waiver of any other right hereunder or of any other breach or failure by said
other Party whether of a similar nature or otherwise.

11.12 Counterparts.  This Agreement may be executed in two or more
      ------------
counterparts, each of which shall be deemed an original, but all of which
together shall constitute one and the same instrument.

                                      15
<PAGE>

     IN WITNESS WHEREOF, the Parties have executed this Agreement as of the date
first set forth above.
                              CORTEX PHARMACEUTICALS, INC.

                              By:____________________________

                              Name:__________________________

                              Title:_________________________


                              SHIRE HOLDINGS AG

                              By:____________________________

                              Name:__________________________

                              Title:_________________________
<PAGE>

                                 SCHEDULE 1.5

                                      [*]

                SEVEN PAGES OF THIS SCHEDULE HAVE BEEN OMITTED












* CONFIDENTIAL PROVISIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION
<PAGE>

                                SCHEDULE 2.1.1

                               RESEARCH PROGRAM

Shire will conduct a clinical investigation at appropriate clinical research
centres of CX516 in adult subjects with a diagnosis of ADHD. The intention of
the study will be to characterize the effect of CX516 on the manifestations of
ADHD. ADHD adult subjects should be in an age range of 18-60 years and adequate
subject numbers would be 30 patients in the CX516 and placebo groups,
respectively. The study period is expected to be 28 days.

The study will be designed in a way that will demonstrate the presence and
magnitude of effects on core and related ADHD symptoms.

The primary outcome scales will be CGI-ADHD and the ADHD rating scale. In
addition, neurocognitive measures of attention and memory are generally
included. These do not have to be identified, but the language should specify a
neuropsychologic test battery for attention and recall will be employed.

Investigators will be selected on the basis of known capabilities in conducting
clinical studies in ADHD. The clinical study will be conducted under an IND, and
adherence to GCP will be monitored.

It is anticipated, subject to regulatory approval and the availability of
appropriate clinical study materials, that IRB approval, subject enrollment,
study conduct, data correction and collection, analysis and reporting of the
study results should occur within a 15 month period subsequent to the IND
filing.

                                      18
<PAGE>

                                SCHEDULE 3.2.1

                                      [*]

                THREE PAGES OF THIS SCHEDULE HAVE BEEN OMITTED





* CONFIDENTIAL PROVISIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION
<PAGE>

                                                                  EXECUTION COPY
                                                                  April 19, 2000


                         CONFIDENTIAL PORTIONS OMITTED
                         -----------------------------



                                   EXHIBIT A

                       DEVELOPMENT AND LICENSE AGREEMENT

                                    between

                          CORTEX PHARMACEUTICALS, INC.

                                      and

                               SHIRE HOLDINGS AG,

                           dated as of April 19, 2000
<PAGE>

                       DEVELOPMENT AND LICENSE AGREEMENT

          THIS DEVELOPMENT AND LICENSE AGREEMENT (the "Agreement") dated as of
___________, 2000 (the "Effective Date") is made between CORTEX PHARMACEUTICALS,
INC., having its principal offices at 15241 Barranca Parkway, Irvine, California
U.S.A., ("Cortex") and SHIRE HOLDINGS AG, plc, having its principal offices at
Bundesstrasse 5, 6300 Zug, Switzerland ("Shire").

                                R E C I T A L S

     A. Cortex possesses know-how, expertise and rights to issued United States
patents and patent applications and corresponding foreign filed patent
applications pertaining to a class of proprietary pharmaceuticals called
"Ampakines(R)".

     B. Certain of these Ampakines(R) have the potential to modulate and treat
ADHD (as defined below).

     C. Cortex and Shire have entered into an Option Agreement dated April 19,
2000, under which Shire investigated the potential usefulness of CX516 for ADHD
and subsequently exercised its option to enter into this exclusive license to
use the Cortex Patent Rights and Cortex Technology (as defined below) to
develop, manufacture and commercialize Ampakines(R) for the treatment of ADHD.

     NOW THEREFORE, in consideration of the premises and of the covenants herein
contained, the parties hereto mutually agree as follows:

1.   DEFINITIONS

     For purposes of this Agreement, the terms defined in this Article shall
have the meanings specified below:

     1.1 "Affiliate" shall mean any corporation or other entity which controls,
          ---------
is controlled by, or is under common control with a Party to this Agreement. A
corporation or other entity shall be regarded as in control of or controlled by
another corporation or entity if it owns or directly or indirectly controls more
than fifty percent (50%) of the voting stock or other ownership interest of the
other corporation or entity, or if it possesses, directly or indirectly, the
power to direct or cause the direction of the management and policies of the
corporation or other entity or the power to elect or appoint fifty percent (50%)
or more of the members of the governing body of the corporation or other entity.

     1.2 "ADHD" shall mean Attention Deficit/Hyperactivity Disorders as defined
          ----
in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, as
may be amended from time to time.

     1.3 "Ampakines(R)" shall mean those compounds that are positive modulators
          ------------
of AMPA-receptor function and which are covered by the Cortex Patents and/or
incorporate, use or were developed with the Cortex Technology.

"Collaboration Compounds" shall have the meaning set forth in Section 3.4.2.
 -----------------------
<PAGE>

     1.4 "Combination Products" shall mean a Product comprised of two or more
          --------------------
pharmaceutically active ingredients, one of which is an Ampakine(R).

     1.5 "Cortex Compounds" shall have the meaning set forth in Section 3.4.1.
          ----------------

     1.6 "Cortex Patent Rights" shall mean all rights useful in the Field under
          --------------------
present and future, foreign and domestic, patents, patent applications, patent
extensions, certificates of invention and applications for certificates of
invention, together with any originals, provisionals, divisionals, continuations
or continuations-in-part, extensions, renewals and reissues owned by, or
licensed to Cortex. Cortex Patent Rights as of the Effective Date, and all
licenses relating to such Cortex Patent Rights are listed in Schedule 1.7
                                                             ------------
hereto.

     1.7 "Customers" shall mean any Third Party, other than a sublicensee of
          ---------
Shire, to whom Shire supplies the Product.

     1.8 "Cortex Technology" shall mean all present and future inventions, trade
          -----------------
secrets, know-how, copyrights, data, regulatory submissions or other
intellectual property of any kind useful in the Field (including any proprietary
biological materials, compounds or reagents) and all confidential technical
information in the possession of Cortex as of the Effective Date and during the
term of this Agreement necessary or useful for the discovery, development,
manufacture, use or sale of a Product.

     1.9  "CX 516" shall mean 1-(Quinoxalin-6-ylcarbonyl) piperdine, the
           ------
specifications of which are attached as Schedule 1.10.

     1.10 "Data" shall have the meaning set forth in Section 2.3.1.
           ----

     1.11 "Development Base Timeline" shall mean the development items and times
           -------------------------
set forth on Schedule 1.12.

     1.12 "Effective Date" shall mean the date first set forth above.
           --------------

     1.13 "Development Phase" shall be, in relation to each Lead Compound, that
           -----------------
period commencing upon the implementation of the Development Plan and continuing
until the first regulatory approval is obtained for that Lead Compound.

     1.14 "Development Plan" shall mean the plan for conducting the development
           ----------------
of a Lead Compound, as may be amended from time to time and as more particularly
described in Section 4.2 below.

     1.15 "Europe" shall mean Austria, Belgium, Switzerland and Liechtenstein,
           ------
Germany, Denmark, Spain, France, the United Kingdom, Greece, Ireland, Italy,
Luxembourg, Monaco, Netherlands, Portugal, Sweden and any other State which is a
Contracting State of both the European Patent Convention and of the Patent
Cooperation Treaty.

     1.16 "FDA" shall mean the Food and Drug Administration of the United States
           ---
of America.

     1.17 "Field" shall mean the use of Ampakines(R) for the treatment of ADHD.
           -----
                                       2
<PAGE>

     1.18 "First Commercial Sale" of any Product shall mean the first sale for
           ---------------------
administration to human patients of such Product in a country after required
regulatory marketing and pricing approval has been granted by the governing
health authority of such country.

     1.19 "FTE" means the full time equivalent effort, for one year, of one
           ---
person who participates directly and effectively in the research activities
contemplated under this Agreement.

     1.20 "Inventions," "Cortex Inventions" and "Shire Inventions" shall have
           ----------    -----------------       ----------------
the meanings set forth respectively in Section 9.1.1.

     1.21 "Joint Inventions" shall have the meaning set forth in Section 9.1.1.
           ----------------

     1.22 "Joint Patent Rights" shall mean all foreign and domestic patents,
           -------------------
patent applications, patent extensions, certificates of invention, together with
any divisions, continuations or continuations-in-part covering Joint Inventions.

     1.23 "Major Country" shall mean the United Kingdom, Germany, Italy, France
           -------------
or Spain.

     1.24 "Lead Compound" shall mean those Cortex Compounds or Collaboration
           -------------
Compounds chosen by Shire, pursuant to Section 3.4.

     1.25 "NDA" shall mean a new drug application filed with the FDA after
           ---
completion of human clinical trials to obtain marketing approval for a Product
in the United States or any comparable application filed with the regulatory
authorities of a country other than the United States to obtain marketing
approval for a Product in that country.

     1.26 "Net Sales" with respect to any Product shall mean the invoiced sales
           ---------
of all such Product billed to Customers by Shire, its Affiliates, its
sublicensees, its joint venture partners or its co-promoters, less the following
items as applicable to such Product: (a) credits or allowances granted upon
returns, rejections or recalls; (b) freight, shipping and insurance costs; (c)
quantity and other trade discounts, credits or allowances actually allowed and
taken; (d) customs duties, taxes and surcharges and other governmental charges
incurred in connection with exportation or importation; (e) bad debts directly
related to the sale of Products, but not to exceed nine-tenths of one percent
(0.9%) and (f) government mandated rebates. The transfer of any Product by Shire
or one of its Affiliates to another Affiliate or sub-licensee of Shire shall not
be considered a sale; in such cases, Net Sales shall be determined based on the
invoiced sales price by the Affiliate or sub-licensee to its customer, less the
deductions allowed under this Section.

          1.26.1  In the event Shire transfers Products for consideration, in
whole or in part, other than cash, the Net Sales price for such Products shall
be deemed to be the weighted average Net Sales cash price then being invoiced by
Shire, its Affiliate or sub-licensee in arms-length transactions with similar
customers in that country.  In no event shall Net Sales of Product be deemed to
occur in the case of transfers of reasonable quantities of samples or clinical
research supplies or similar transfers.

          1.26.2  The Net Sales of Combination Products shall be calculated by
multiplying the standard invoice price for the Combination Product by a
fraction, the numerator of which shall be invoice price for the Product (based
on the same formulation sold separately), and the denominator of which shall be
the invoice price of the Combined Product.

                                       3
<PAGE>

     1.27 "Party" shall mean Cortex or Shire.
           -----

     1.28 "Phase I, Phase II and Phase III Studies" shall mean clinical studies,
           ---------------------------------------
as described in Section 312.21 of the FDA's regulations regarding
Investigational New Drug Applications (21 C.F.R. 312.21), as of the date hereof
and attached as Schedule 1.29 hereto.

     1.29 "Product" shall mean any therapeutic composition for administration to
           -------
human subjects containing an Ampakine(R) as a pharmaceutically active ingredient
for use in the Field.

     1.30 "Quarter" means each calendar quarter commencing on January 1, April
           -------
1, July and 1 October.

     1.31 "Research Funding Payment" shall the meaning set forth in Section 7.2.
           ------------------------

     1.32 "Research Management Committee" shall mean the joint committee
           -----------------------------
composed of representatives of Cortex and Shire described in Article 5 hereof.

     1.33 "Research Phase" shall be for a period of two (2) years from the date
           --------------
of commencement of the Research Plan unless otherwise extended pursuant to
Section 3.1.

     1.34 "Research Plan" shall mean the plan for identifying and evaluating
           -------------
potential Ampakines(R) with applicability in the Field, as amended from time to
time by the Research Management Committee, which plan, including all amendments,
shall be attached to this Agreement as Schedule 1.35.
                                       -------------

     1.35 "Shire Data" shall have the meaning set forth in Section 2.3.1.
           ----------

     1.36 "Stock Purchase Agreement" shall mean the agreement between the
           ------------------------
Parties for Shire to invest in the Common Stock of Cortex on the terms set forth
in the form of Exhibit D hereto.
               ---------

     1.37 "Third Party" shall mean any entity other than Cortex or Shire and
           -----------
their respective Affiliates.

     1.38 "Third Party Licenses" shall have the meaning set forth in Section
           --------------------
12.3.1 and Exhibit F hereto.
           ---------

     1.39 "Valid Claim" shall mean with respect to the Product any claim of any
           -----------
issued and unexpired patent or pending patent application included within the
Cortex Patent Rights which has not been held, disallowed, revoked, unenforceable
or invalid by a final, unappealable decision of a court or other governmental
agency of competent jurisdiction, and which has not been admitted to be invalid
or unenforceable through re-issue, disclaimer or otherwise, unless and until
reinstated.

2.   SCOPE AND STRUCTURE OF THE COLLABORATION

     2.1  General.  Cortex and Shire wish to establish a collaborative alliance
          -------
relative to the Field and, in particular, to conduct the Research Plan and the
Development Plan, as more particularly set out in Articles 3, 4 and 5 below.
The purpose of the Research Plan shall be to identify and/or develop
Ampakines(R) with applicability in the Field as more particularly set out
therein.  During the Research Phase and the Development Phase, Cortex and Shire
shall communicate regularly as to the

                                       4
<PAGE>

status and progress of each so that Shire may reasonably evaluate the potential
value of any Ampakines(R) in the Field.

     2.2  Exclusivity.  Shire acknowledges that Cortex is free to engage in
          -----------
activities outside the Field, either on its own behalf and for the benefit of
Third Parties.  Each of Cortex and Shire agree that, except as set forth in this
Agreement, it will not engage in any activities in the Field with or on behalf
of any Third Party.

     2.3  Data.
          ----

          2.3.1  Collaboration Data.  Cortex shall use good scientific
                 ------------------
practices, and Shire shall use reasonable efforts to comply in all material
respects with applicable regulations and customary good clinical practices in
the performance of the Research Plan and Development Plan hereunder (including
all data in the form required to be maintained under any applicable governmental
regulations).  Such records shall comprise books, results, reports, research
notes, charts, graphs, comments, computations, analyses, recordings,
photographs, computer programs and documentation thereof, computer information
storage means, samples of materials and other graphic or written data generated
in connection with the Research Plan and Development Plan.  Any such data
developed by employees of Cortex, or others on behalf of Cortex, shall be owned
by Cortex ("Cortex Data") and any such data developed by employees of Shire, or
others on behalf of Shire, shall be owned by Shire ("Shire Data").  Each Party
shall provide the other Party the right to inspect its Data, and shall provide
summaries of its Data, to the extent reasonably required for the performance of
each Party's obligations under this Agreement; provided, however, that each
Party shall maintain such records and the information of the other Party
contained therein in confidence in accordance with Article 10 below and shall
not use such records or information of the other Party except to the extent
otherwise permitted by this Agreement.

          2.3.2  Adverse Event Reports.  Each Party shall promptly report to the
                 ---------------------
other potentially serious or unexpected adverse events (including adverse drug
experiences, as defined in 21 C.F.R. (S) 314.80 or other applicable regulations)
with respect to Ampakines(R) of which it becomes aware and in no event later
than five (5) days after initial receipt of the information by such party, with
the exception of Life-Threatening Adverse Drug Experiences (as defined in 21
C.F.R. (S) 314.80(a)), which shall be notified to the other Party within 24
hours of knowledge of the notifying Party.  Each Party shall report to the other
Party summaries of other adverse events with respect to every twelve (12)
months.  Cortex may provide such information that it receives from Shire under
this Section 2.3.2 to its other licensees.  Cortex shall use commercially
reasonable efforts to include in its other agreements, similar provisions to
this Section 2.3.2.

3.   RESEARCH PHASE

     3.1  Term of the Research Phase.  Cortex shall use all reasonable endeavors
          --------------------------
to comply with the terms of the Research Plan and to conduct the Research Plan
within the Research Phase.  The Research Phase shall commence as soon as is
reasonably practicable following the Effective Date and be for a period of two
(2) years from that date, or such longer period as the Parties may agree, taking
into account all relevant factors, including the progress of the Research Plan.

     3.2  Research Plan.  The Research Plan shall be conducted by Cortex in good
          -------------
scientific manner, and in compliance with all applicable legal requirements.
The Research Plan will be updated and approved as the Research Management
Committee sees fit, but in no event, later than

                                       5
<PAGE>

thirty (30) days prior to the start of each year during the Research Phase. The
Research Plan in effect at any time may not be amended except as agreed in
writing by the Research Management Committee. If at any time during the Research
Phase either Party determines that a change to the Research Plan would be
beneficial to the collaboration of the Parties, such Party shall prepare and
submit to the Research Management Committee a written proposal detailing its
proposed changes to the Research Plan. At its next meeting, the Research
Management Committee shall consider any such proposal.

     3.3  Subcontracts. Cortex may subcontract portions of the Research Plan to
          ------------
be performed by it in the normal course of its business to Third Parties with
the prior consent of the Research Management Committee; provided, however, that
Cortex shall require such Third Parties to enter into appropriate
confidentiality agreements unless such subcontracting would not require the
transfer of confidential Information (as defined in Article 10 hereof) to the
Third Party.

     3.4  Compound Selection.
          ------------------

          3.4.1  Cortex Compounds.  At the commencement of the Research Phase,
                 ----------------
Cortex will promptly provide to the Research Management Committee details of the
chemical structure and properties for CX516 (to the extent not already disclosed
under the Option Agreement), and no less than [*] additional Ampakines(R) for
which Cortex then has the right to grant the licenses herein to Shire and which
Cortex believes will be useful in the Field, selected in accordance with the
criteria determined pursuant to Section 3.4 of the Option Agreement, (the
"Cortex Compounds").  During the term of the Research Phase, Cortex shall
evaluate such additional compounds as to which it has the right to grant the
licenses herein to Shire to determine if such compounds would be useful in the
Field.  If Cortex determines that such compounds may be more useful in the Field
than the previously selected Cortex Compounds, it shall so inform the Research
Management Committee, and Shire.  Shire may, at its discretion, substitute one
of such new compounds for one of the [*] existing Cortex Compounds, in which
case such compound shall become a Cortex Compound and such replaced compound
shall become available to Cortex for development or commercialization by it or a
Third Party.  Cortex will keep these Cortex Compounds available to Shire for
selection as a Lead Compound for a period of three (3) months from the
commencement of the Research Phase, and shall not, during such period, grant to
any Third Party rights to develop and commercialize such compounds.  Shire may
select, by notice in writing to Cortex, up to [*] such Cortex Compounds as Lead
Compounds.  At the end of the three (3) month period, any Cortex Compound not
selected as a Lead Compound shall become available to Cortex for development and
commercialization by it or a Third Party.







* CONFIDENTIAL PROVISIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION

                                       6
<PAGE>

          3.4.2  Collaboration Compounds.  In accordance with the Research Plan,
                 -----------------------
Cortex will synthesize and evaluate additional compounds with potential activity
in the Field (the "Collaboration Compounds").  Upon development of each
Collaboration Compound, Cortex will promptly supply Shire with such information
and materials in its possession which is reasonably necessary or useful to
enable Shire to evaluate the activity of the Collaboration Compound in the
Field, including details of the application of the selection criteria summarized
in Section 3.4 of the Option Agreement.  Cortex will keep these Collaboration
Compounds available to Shire for selection as a Lead Compound for a period of
[*] from the end of the Research Phase.  Based upon information developed by
Cortex with respect to such compounds, Shire may select, prior to the end of
such period by notice in writing to Cortex, up to [*] such Collaboration
Compounds, less the number of Cortex Compounds selected as Lead Compounds under
Section 3.4.1.  At the end of the twelve (12) month period, any Collaboration
Compound not selected as a Lead Compound will become available to Cortex for
development and commercialization by it or a Third Party.

          3.4.3  Substitution of Lead Compounds.  Subject to the provisions of
                 ------------------------------
this Section 3.4, Shire may return to Cortex any Lead Compound it has selected,
in exchange for a different Cortex Compound or Collaboration Compound, if Cortex
is able, at such time, to grant the rights set forth herein with respect to such
compound.  Upon such selection, such compound shall become a Lead Compound.

          3.4.4  Return of Lead Compounds to Cortex.  Upon commencement of a
                 ----------------------------------
Phase III Study by Shire for the first Product, Shire shall deselect Lead
Compounds such that it retains no more than [*] Lead Compounds and any so
deselected compounds shall be returned to Cortex.  Upon filing of the NDA by
Shire in the United States, Shire shall deselect Lead Compounds such that it
retains no more than [*] Lead Compounds and any compounds so deselected shall be
returned to Cortex.  Upon the approval by the FDA of the first Product for
commercialization in the United States, Shire shall deselect Lead Compounds such
that it retains no more than [*] Lead Compounds and any so deselected compounds
shall be returned to Cortex.  The choice of which Lead Compounds to deselect by
Shire pursuant to this Section 3 shall be at Shire's sole discretion.  All
rights to deselected Compounds shall revert immediately back to Cortex, and
Cortex shall be free to use all such compounds for all purposes and may grant
rights to such compounds to Third Parties for use outside, but not inside, the
Field.  When rights to a Lead Compound reverts to Cortex pursuant to this
Section 3.4, Shire agrees, at the cost of Cortex, to execute and deliver such
instruments and take such other actions as Cortex shall reasonably request in
order to carry out the transfer of such rights to Cortex.

     3.5  Availability of Employees.  Each Party agrees to make its employees
          -------------------------
and nonemployee consultants reasonably available at their respective places of
employment to consult with the other Party on issues arising during the Research
Phase and in connection with any request from any regulatory agency, including
regulatory, scientific, technical and clinical testing issues.  If Shire
requests Cortex personnel to consult other than at Cortex's facility, Shire
shall reimburse Cortex the reasonable travel and lodging expenses of such
personnel.



* CONFIDENTIAL PROVISIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION

                                       7
<PAGE>

     3.6  Visit of Facilities.  Representatives of Shire may, upon reasonable
          -------------------
notice and at times reasonably acceptable to Cortex, visit Cortex's facilities
where the Research Plan is being implemented, and consult informally, during
such visits and by telephone, with Cortex's personnel performing work on the
Research Plan.  Shire's representative shall abide by all reasonable operating
procedures and rules of Cortex's facilities with respect to safety and
confidentiality.

4.   DEVELOPMENT PHASE

     4.1  Term of the Development Phase.  The term of the Development Phase
          -----------------------------
shall be, in relation to each Lead Compound, that period commencing upon the
implementation of the Development Plan and continuing until the first regulatory
approval is obtained for that Lead Compound.

     4.2  Development Plan.  After selection of each Lead Compound, Shire shall
          ----------------
prepare and deliver to Cortex within a reasonable period, such period not to
exceed [*] days, thereafter, the Development Plan for conducting further
development on such Lead Compound, describing the activities necessary to obtain
regulatory approval for such Lead Compound.  Each such Development Plan shall be
prepared by Shire in a manner consistent with commercially reasonable standards
and practices in the industry.  The content, timing and priorities in any
Development Plan shall be subject to Shire's discretion.  Cortex may provide
suggestions to Shire with respect to each Development Plan.

     4.3  Development of Lead Compounds, Diligence.
          ----------------------------------------

          4.3.1  Development Plans.  Shire shall have the sole responsibility
                 -----------------
for conducting development of the Lead Compounds pursuant to each respective
Development Plan.  Each Development Plan shall be designed by Shire and may be
amended, postponed or terminated at Shire's sole discretion, provided that Shire
shall use reasonable commercial diligence to develop and commercialize at least
one Lead Compound.

          4.3.2  Development Base Timeline.  In order to fulfil its obligations
                 -------------------------
referred to in Section 4.3.1 above, Shire shall, for at least one Lead Compound,
comply with the Development Base Timeline set out in Schedule 1.12 hereto,
provided that Shire may extend such projected timelines to such extent as may be
necessary if:

               4.3.2.1  required for safety or other regulatory reasons;

               4.3.2.2  directly attributable to any failure or delay on the
part of Cortex in meeting its obligations hereunder; or

               4.3.2.3  necessitated as a direct result of the assumptions set
out in the Development Base Timeline not being met.


* CONFIDENTIAL PROVISIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION

                                       8
<PAGE>

     4.4  Diligence Meaning.  For the purposes of Section 4.3 above, "reasonable
          -----------------
commercial diligence" means reasonable efforts consistent with Shire's normal
business practice, being commensurate with the level of effort used by Shire
and/or its Affiliates in connection with other Shire products of similar
importance which Shire and/or its Affiliates intend to develop for sale in
strategic territories world-wide (based on such criteria as patient population,
price per treatment and competitive position), and in a manner consistent with
accepted best practice in the pharmaceutical industry.

     4.5  Supply of Lead Compounds.  Shire will be responsible for providing, at
          ------------------------
its own expense, the supply of all Lead Compounds necessary for the conduct of
the Development Plan.  Shire may contract with Cortex under terms mutually
agreed upon between the Parties, to provide additional services.  Shire agrees
to use commercially reasonable efforts to conduct the Development Phase.

5.   MANAGEMENT OF THE RESEARCH PROGRAM

     5.1  Research Management Committee.
          -----------------------------

          5.1.1  Formation and Composition.  A joint committee comprised of two
                 -------------------------
(2) named representatives of each of Shire and of Cortex, (the "Research
Management Committee") shall be appointed promptly after the date hereof and
shall meet as needed, but not less than once each quarter during the Research
Phase, and not less than semi-annually during the Development Phase.  Such
meetings shall be at such times agreed to by Cortex and Shire, at such locations
or in such other form (e.g., telephone or video conference) as the members of
the Research Management Committee shall agree.

          5.1.2  Functions and Powers.  The principal functions of the Research
                 --------------------
Management Committee will be to (i) discuss and approve the Research Plan in
accordance with Section 3.2, (ii) manage the ongoing research and development
investigations conducted under the Research Plan including the utilization of
FTE's, (iii) monitor the progress and results of such investigations, (iv)
consider and make any necessary or desirable amendments to the Research Plan,
and (v) monitor the Development Plan.  After conclusion of the Research Phase
and during the Development Phase, the Research Management Committee shall
continue to operate to serve as a liaison between Cortex and Shire.  The
Research Management Committee shall endeavor in good faith to make decisions
unanimously, failing which the procedure set out in Section 5.3 shall apply.

          5.1.3  Members; Approval; Chair.  A Party may change one or more of
                 ------------------------
its representatives to the Research Management Committee at any time.  Members
of the Research Management Committee may be represented at any meeting by
another member of the Research Management Committee, or by a deputy.  Either
Party may permit additional employees and consultants to attend and participate
(on a non-voting basis) in the Research Management Committee meetings, subject
to the confidentiality provisions of Article 10.  Any approval, determination or
other action agreed to by all of the members of the Research Management
Committee or their deputies present at the relevant Research Management
Committee meeting shall be the approval, determination or other action of the
Research Management Committee, provided that at least one representative of each
Party is present at such meeting.  The Research Management Committee shall be
chaired by a Shire representative to the committee.

                                       9
<PAGE>

          5.1.4  Minutes and Reports.  The Research Management Committee shall
                 -------------------
be responsible for keeping accurate minutes of its deliberations which record
all proposed decisions and all actions recommended or taken.  After approval,
such minutes must be signed by each member of the Research Management Committee.
Within twenty-one (21) days of each meeting, the Chair shall provide the Parties
with minutes of such meeting, a summary of the work and progress to date, any
issues requiring resolution and any proposed decisions and actions taken, to all
members of the Research Management Committee.  All records of the Research
Management Committee shall be available to both Parties.

          5.1.5  Information and Results.  Except as otherwise provided, the
                 -----------------------
Parties will make available and disclose to one another all results of the work
conducted pursuant to the Research Plan and Development Plan(s) prior to and in
preparation for Research Management Committee meetings, in the form and format
to be designated by the Research Management Committee.

     5.2  Reports to the Research Management Committee.  Within thirty (30) days
          --------------------------------------------
following the end of each Quarter from commencement of the Research Phase until
conclusion of the Research Phase and within thirty (30) days following the end
of every two (2) Quarters until the conclusion of the Development Phase, each
Party shall provide to the members of the Research Management Committee a
written report, in a format to be approved by the Research Management Committee,
which shall summarize in reasonable detail the work it has performed during the
preceding period.

     5.3  General Disagreements.  All disagreements within the Research
          ---------------------
Management Committee shall be subject to the following:

               5.3.1.1 The representatives to the Committee will negotiate in
good faith for a period of not more than sixty (60) days to attempt to resolve
the dispute;

               5.3.1.2   If the representatives of the Committee are unable to
resolve the dispute in accordance with subsection (a) above, then they shall
promptly present the disagreement to the Chief Executive Officer of Shire and
the Chief Executive Officer of Cortex;

               5.3.1.3   Promptly thereafter, such executives shall discuss each
Party's view and explain the basis for such disagreement; and

          If such executives cannot promptly resolve such disagreement within
sixty (60) days after such issue has been referred to them, then such disputes
shall be referred to arbitration as described in Section 15.6.

6.   LICENSES

     6.1  Grant of Research License by Shire.  Shire hereby grants to Cortex the
          ----------------------------------
worldwide exclusive right and license in the Field under the Shire Data, Shire
Inventions and Shire's interest in Joint Patent Rights and Joint Inventions to
the extent necessary or useful to carry out Cortex's research responsibilities
under the Research Plan in accordance with this Agreement.

     6.2  Grant of Research License by Cortex.  Cortex hereby grants to Shire
          -----------------------------------
the worldwide exclusive right and license in the Field under the Cortex Patent
Rights, Cortex Technology, Cortex Inventions and Cortex's interest in Joint
Patent Rights and Joint Inventions to the extent necessary or

                                      10
<PAGE>

useful to carry out Shire's development responsibilities under the Development
Plan(s) in accordance with this Agreement.

     6.3  Grant of Commercialization License. Cortex hereby grants to Shire,
          ----------------------------------
under the Cortex Patent Rights, Cortex Technology, Cortex Inventions and
Cortex's interest in Joint Patent Rights and Joint Inventions, subject to
Section 6.4 below, the worldwide exclusive right and license (with the full
right to sublicense) inside the Field to further develop, manufacture, have
manufactured, use, commercialize, distribute for sale and sell Products
containing Lead Compounds, such license to become effective upon selection of
such Lead Compounds by Shire under Section 3.4.  Shire shall notify Cortex of
any sublicense of the rights granted herein to a non-Affiliate of Shire within
thirty (30) days of entering into such sublicense.

     6.4  Reserved Rights.  Cortex at all times reserves the right under the
          ---------------
Cortex Patent Rights, Cortex Technology, Cortex Inventions and Cortex's interest
in Joint Patent Rights and Joint Inventions to make and use Ampakines(R) in
order to carry out its obligations under this Agreement in accordance with the
Research Plan.

7.   PAYMENTS

     7.1  License Fee, Stock Purchase.  Upon the execution of this Agreement,
          ---------------------------
Shire shall make a payment to Cortex of [*] by wire transfer to an account
designated by Cortex.  In addition, Shire shall purchase [*] of Cortex Common
Stock as set forth in the Stock Purchase Agreement.  In the event that at the
time of execution of this Agreement, Cortex's rights and obligations under this
Agreement have been assumed by a successor entity by way of acquisition of
Cortex or otherwise, and such successor's equity securities are publicly traded,
Shire shall have the right to purchase such equity securities on the terms set
forth in the Stock Purchase Agreement.  In the event the equity securities of
such successor are not publicly traded, Shire shall pay an additional [*] as a
License Fee and shall not purchase any such equity securities.  Payments made to
Cortex pursuant to this Section 7.1 shall not be credited any other payment
otherwise due Cortex under this Article 7.

     7.2  Funding of Research Program by Shire.
          ------------------------------------

          7.2.1  FTE Equivalents Funding.  In consideration of Cortex's
                 -----------------------
performance of its obligations under the Research Plan, Shire shall fund up to
[*] FTE's for Cortex (onsite or offsite) at the cost of [*] per FTE per year for
a period of two (2) years from the commencement of the Research Plan.  Such
FTE's shall include a balanced group of Ph.D.s or equivalent and other
scientists as described in the Research Plan.  The amounts payable shall be paid
by wire transfer in United States dollars in four equal payments paid Quarterly,
in advance, by the tenth (10th) business day of each Quarter, pro-rated as
necessary for the first and last Quarter (each such payment referred to as a
"Research Funding Payment").  The first Research Funding Payment shall be paid
within ten (10) days of the commencement of the Research Phase.  Research
Funding Payments shall not be credited against any other payment otherwise due
Cortex under this Article 7.  Except as otherwise agreed by the Parties, or set
forth in this Section 7.2, each Party shall bear all of its costs incurred in
connection with the Research Program.

* CONFIDENTIAL PROVISIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION

                                      11
<PAGE>

          7.2.2    FTE Record Keeping. Cortex will keep records of the time
                   ------------------
spent by its FTEs on the Research Plan. Cortex will report the level of FTE
efforts to the Research Management Committee on a Quarterly basis. Shire shall
have the right to have these records audited, in the same manner as is set forth
in Section 7.5.4. During the course of the Research Program, Cortex will notify
Shire if it becomes apparent that the level of effort required under the
Research Program is expected to deviate from the level required under Section
7.2. At the end of each year of the Research Term, the Parties will restore any
imbalance between actual and funded FTEs either through appropriate payments or
refunds. However, Shire's prior written consent must be obtained if the actual
FTE effort spent will exceed by more than 10% the costs allocated pursuant to
Section 7.2.1 above.

     7.3  Manufacturing.  Shire, at its own cost, shall manufacture or shall
          -------------
procure Lead Compounds for utilization during the Research Phase and the
Development Phase.  Cortex will, at its own cost, provide technical assistance
as reasonably requested by Shire.

     7.4  Milestones.
          ----------

          7.4.1    Milestone Payments.  In consideration of the licenses granted
                   ------------------
to Shire hereunder, Shire shall pay the following amounts to Cortex upon the
achievement (prior to the expiration or termination of this Agreement pursuant
to Article 14 hereof) of each of the applicable milestones:

          [*]

*For purposes hereof, First Patient Dosing shall mean the time at which the
first dose is given to the first patient in the clinical study.

          Each milestone payment shall be paid once only, even if such milestone
is met on more than one occasion.

Shire shall promptly notify Cortex in writing of the occurrence of the
milestones set forth above.  Within thirty (30) days after the occurrence of
such milestone, Shire shall pay to Cortex by wire transfer or other means
reasonably acceptable to Cortex and Shire, the milestone payments set forth
above.  Payments made to Cortex pursuant to this Section 7.4 shall not be
credited against any other payments under this Article 7.

     7.5  Royalties on Net Sales.
          ----------------------

          7.5.1    Royalty Rate.  In consideration of the licenses granted to
                   ------------
Shire pursuant to Article 5 hereof, Shire shall pay Cortex either:

          7.5.1.1  the following royalties on Net Sales of Product in any
country where the sale of Product would infringe a Valid Claim of the Cortex
Patents or the Joint Patent Rights, but for the grant of the license hereunder:

     [*]

          or

* CONFIDENTIAL PROVISIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION

                                      12
<PAGE>

          7.5.1.2  The following royalties on Net Sales of Product where sale of
Product in that country are not subject to a Valid Claim in any Cortex Patent:

     [*]

          7.5.2    Third Party Royalties.  In the event that it is necessary for
                   ---------------------
Shire to license intellectual property or other proprietary rights from a Third
Party to develop, use, make or sell Products in any country, the royalties
otherwise payable under this Section 7.5 shall be reduced by [*] the sum of
royalties payable to such third parties, provided however, that in no event
shall the aggregate royalties on Net Sales payable to Cortex with respect to
such country be reduced to less than [*] of the Net Sales as a result of the
adjustment in this Section 7.5.2.

          7.5.3    Royalty Reports, Exchange Rates.  During the term of this
                   -------------------------------
Agreement, following the First Commercial Sale of a Product in any country by
Shire, Shire shall furnish to Cortex a written Quarterly report showing, on a
country by country basis: (i) the gross sales of all Products sold by Shire and
its Affiliates and its sublicensees during the reporting period and the
calculation of Net Sales from such gross sales; (ii) the royalties and other
payments payable in United States dollars which shall have accrued hereunder in
respect of such sales; (iii) withholding taxes, if any, required by law to be
deducted in respect of such sales, as applicable; (iv) the dates of the First
Commercial Sales of any Products in any country by Shire and its Affiliates and
its sublicensees during the reporting period; and (v) the exchange rates used in
determining the amount of United States dollars.  All amounts payable will first
be calculated in the currency of sale and then converted into United States
dollars using as a rate of exchange the average exchange rate reported in the
Wall Street Journal during the Quarter to which the payment relates.  Reports
together with the royalty payable for the periods to which the reports relate
shall be due on the forty-fifth (45th) day following the close of each Quarter.
If no royalty is due for any royalty period hereunder, Shire shall so report.
Shire shall keep complete and accurate records in sufficient detail to properly
reflect all gross sales and Net Sales and to enable the royalties payable
hereunder to be determined.

          7.5.4    Audits.  Upon the written request of Cortex, Shire shall
                   ------
permit an independent public accountant selected by Cortex and acceptable to
Shire, which acceptance shall not be unreasonably withheld or delayed, to have
access during normal business hours to such of the records of Shire as may be
reasonably necessary to verify the accuracy of the royalty reports hereunder in
respect of any fiscal year ending not more than twenty-four (24) months prior to
the date of such request. All such verifications shall be conducted at the
expense of Cortex and not more than once in each calendar year.

          In the event such accountant concludes that additional royalties were
owed during such period, the additional royalty shall be paid within thirty (30)
days of the date Cortex delivers to Shire such accountant's written report so
concluding.  The fees charged by such accountant shall be paid by Cortex unless
the audit discloses that the royalties payable by Shire for the audited period
are more than one hundred and five percent (105%) of the royalties actually paid
for such period, in which case Shire shall pay the reasonable fees and expenses
charged by the accountant.

* CONFIDENTIAL PROVISIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION

                                      13
<PAGE>

          Shire shall include in each sublicense granted by it pursuant to this
Agreement a provision requiring the sublicensee to make reports to Shire, to
keep and maintain records of sales made pursuant to such sublicense and to grant
access to such records by Cortex's independent accountant to the same extent
required of Shire under this Agreement.  Upon the expiration of twenty-four (24)
months following the end of any calendar year, the calculation of royalties
payable with respect to such year shall be binding and conclusive upon Cortex;
and Shire and its sublicensees shall be released from any liability or
accountability with respect to royalties for such year.

          Cortex agrees that all information subject to review under this
Section 7.5.4 or under any sublicense agreement is confidential and that it
shall cause its accountant to retain all such information in confidence.

          7.5.5  Royalty Payment Terms.  Royalties shown to have accrued by each
                 ---------------------
royalty report provided for under this Agreement shall be due and payable on the
date such royalty report is due.  Payment of royalties in whole or in part may
be made in advance of such due date.  Royalties determined to be owing, and any
overpayments to be credited, with respect to any prior quarter shall be added,
or credited, as the case may be, together with interest thereon accruing under
this Agreement from the date of the report for the quarter for which such
amounts are owing, to the next quarterly payment hereunder.

     7.6  Withholding of Taxes.  Any withholding of taxes levied by tax
          --------------------
authorities outside the United States on the payments hereunder shall be borne
by Cortex and deducted by Shire from the sums otherwise payable by it hereunder
for payment to the proper tax authorities on behalf of Cortex.  Notwithstanding
the previous sentence, earned royalties with respect to sales occurring in any
country outside the United States shall not be reduced by more than [*] by any
taxes, fees or other changes imposed on Cortex by the government of such country
on the remittance of royalty income.  Shire agrees to cooperate with Cortex in
the event Cortex claims exemption from such withholding or seeks deductions
under any double taxation or other similar treaty or agreement from time to time
in force, such cooperation to consist of providing receipts of payment of such
withheld tax or other documents reasonably available to Shire.  If in the
opinion of either Party the provisions of the Section become unduly burdensome,
the Parties agree to meet and discuss such other options as may be available to
them.

     7.7  Exchange Controls.  Except as hereinafter provided in this Section,
          -----------------
all payments to be made pursuant to Article 7 shall be paid in United States
dollars.  If at any time legal restrictions prevent the prompt remittance of
part or all royalties with respect to any country where the Product is sold,
payment shall be made through such lawful means or methods as Shire may
determine.  When in any country the law or regulations prohibit both the
transmittal and deposit of royalties on sales in such a country, royalty
payments shall be suspended for as long as such prohibition is in effect, and as
soon as such prohibition ceases to be in effect, all royalties that Shire or its
sublicensees would have been obligated to transmit or deposit, but for the
prohibition, shall forthwith be deposited or transmitted promptly to the extent
allowable, as the case may be.  If the royalty rate specified in this Agreement
should exceed the permissible rate established in any country, the royalty rate
for sales in such country shall be adjusted to the highest legally permissible
or government-approved rate.

* CONFIDENTIAL PROVISIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION

                                      14
<PAGE>

     7.8  Interest on Late Payments.  Any payments by Shire that are not paid,
          -------------------------
or overpaid, on or before the date such payments are due under this Agreement
shall bear interest, to the extent permitted by applicable law, at two
percentage points above the LIBOR rate calculated on the number of days payment
is delinquent.  LIBOR rate means the interest rate per annum as determined by
Bank of America NT&SA, at which deposits in U.S. dollars are generally available
in the London interbank market with maturities of thirty (30) days.

8.   MARKETING

     8.1  Marketing Plans.  Shire shall prepare and deliver to Cortex an outline
          ---------------
of marketing plans on NDA approval for each Product in the United States, and
each Major Country, prior to the launch of such Product in such country.  Such
plans shall include plans related to the launch, promotion and sale of Products.
Shire shall submit the Marketing Plans annually to Cortex for review and
comment.

     8.2  Product Marking.  Products shall be marked as a product of Shire, and
          ---------------
shall carry the legend:  "Marketed under license from Cortex Pharmaceuticals,
Inc." or such other legend as may be agreed between the parties, subject to
local law and regulation.

9.   INTELLECTUAL PROPERTY RIGHTS

     9.1  Ownership.
          ---------

          9.1.1  Ownership of Inventions.  Inventorship, with respect to
                 -----------------------
inventions made pursuant to the work carried out hereunder shall be determined
in accordance with United States rules of Inventorship.  All right, title and
interest in all writings, inventions, discoveries, improvements and other
technology or constituting a Product, whether or not patentable or
copyrightable, and any patent applications, patents or copyrights based thereon
(collectively, the "Inventions") that are conceived and/or reduced to practice
during and as a result of the work conducted hereunder solely by employees of
Cortex or others acting on behalf of Cortex ("Cortex Inventions") shall be owned
                                                     ----------
by Cortex.  All right, title and interest in all Inventions that are conceived
and/or reduced to practice during and as a result of the work conducted
hereunder solely by employees of Shire or others acting on behalf of Shire
("Shire Inventions") shall be owned by Shire.  Shire Inventions shall include
any Ampakines(R) that are solely invented, conceived or developed by Shire
without utilizing Cortex Patent Rights or Cortex Technology.  All right, title
and interest in all Inventions that are conceived and/or reduced to practice
during and as a result of the work conducted hereunder jointly by employees of
Cortex and Shire (the "Joint Inventions") shall be owned jointly by Shire and
Cortex.

          9.1.2  Cooperation of Employees.  Each Party represents and agrees
                 ------------------------
that (except where such assignment is required by law) all employees or others
acting on its behalf in performing its obligations under this Agreement shall be
obligated under a binding written agreement to assign to such Party, or as such
Party shall direct, all Inventions (including Joint Inventions) made or
conceived by such employee or other person, or in the case of non-employees
working for other companies or institutions on behalf of Cortex or Shire.

     9.2  Provisions Concerning the Filing, Prosecution and Maintenance of
          ----------------------------------------------------------------
Technology, Patent Rights and Joint Inventions.
----------------------------------------------

                                      15
<PAGE>

          9.2.1  Priority Filings for Inventions.  When an Invention with an
                 -------------------------------
application within the Field has been made which may reasonably be considered to
be patentable or when a determination is made that Cortex Technology, or a Joint
Invention utilized in the Research Plan, may reasonably be considered to be
patentable, a priority patent application shall be filed as soon as reasonably
possible.  If Cortex Technology, Cortex Patents Rights, or a Cortex Invention or
a Joint Invention or Joint Patent Right is involved, such application shall be
filed by Cortex, in such countries as reasonably designated by Cortex after
consultation with Shire.  If a Shire Invention is involved, such application may
be filed by Shire, in such countries as reasonably designated by Shire, after
consultation with Cortex.

          9.2.2  Foreign Filing Decisions for Inventions.  No later than nine
                 ---------------------------------------
(9) months following the filing date of a priority patent application filed
according to Section 9.2.1, the Parties shall consult together as to whether
such priority application should be abandoned without replacement; abandoned and
refiled; proceeded with in the country of filing only; or used as the basis for
a claim of priority under the Paris Convention for corresponding applications in
other countries.

          9.2.3  Prosecution and Maintenance.  Cortex shall use its best efforts
                 ---------------------------
to file, prosecute and maintain patent applications and patents covering all
Cortex Technology, Cortex Patent Rights and Joint Inventions in all designated
countries.  For so long as the license set forth in Section 6.3 remains in
effect, Cortex agrees to file, prosecute and maintain such patent applications
and patents in all countries identified on Exhibit E hereto.  Shire may, from
                                           ---------
time to time, by written notice to Cortex, amend in a commercially reasonable
manner Exhibit E.  Cortex shall consult with Shire as to the preparation and
       ---------
filing (if time permits), prosecution and maintenance of such patent
applications and patents, and shall furnish to Shire copies of documents
relevant to such preparation, filing, prosecution or maintenance sufficiently
prior to filing such document or making any payment due thereunder to allow for
review and comment by Shire, and Cortex reasonably shall consider all such
comments.  Cortex shall not abandon claims under the Cortex Patent Rights
without prior notice to Shire.  In the event that Cortex does not file,
prosecute and maintain any such patent application or patent as set forth above,
it shall give Shire forty-five (45) days' notice before any relevant deadline
and transmit all information reasonable and appropriate relating to such patent
application or patent, and Shire shall have the right to pursue, at its own
expense, filing, prosecution and maintenance thereof, in which event Cortex
shall assign all of its rights therein to Shire.

          9.2.4  Patent Costs.  Cortex shall bear the expense of filing,
                 ------------
prosecuting and maintaining patent applications and patents for Cortex Patent
Rights and Cortex Inventions in the Field and (ii) patent applications and
patents for Joint Patent Rights covering Joint Inventions which have application
inside and outside the Field.  Shire shall, to the extent it elects to do so,
bear the expense of filing, prosecuting and maintaining patent applications and
patents covering Shire Inventions.  Shire and Cortex shall equally share the
expense of filing, prosecuting, and maintaining patent applications and patents
for Joint Patent Rights covering Joint Inventions which have application only
inside the Field.

          9.2.5  Failure to Pay for Joint Inventions.
                 -----------------------------------

                 9.2.5.1  If at any time either Party shall elect not to
continue to reimburse the other for its allocated expenses of filing,
prosecuting or maintaining in any country any patent application or patent
included in the Joint Inventions or Joint Patent Rights, it shall so notify the
other Party within thirty (30) days of such determination and thereafter such
Party shall surrender to the other Party its rights and licenses under such
patent or patent application in such country.

                                      16
<PAGE>

                 9.2.5.2  In the event either Party makes an election pursuant
to subsection 9.2.5.1 above, it shall remain obligated to pay for or to
reimburse the other Party for any costs incurred with respect to such patent
application or patent prior to such election.

                 9.2.5.3  Each Party agrees that it will not abandon the
prosecution of any patent applications included within the Joint Inventions or
Joint Patent Rights for which it is responsible nor shall it fail to make any
payment or fail to take any other action necessary to maintain a patent under
the Joint Inventions or Joint Patent Rights unless it has notified the other
Party in sufficient time for such other Party to assume such prosecution or make
such payment.

     9.3  No Other Technology Rights.  Except as otherwise expressly provided in
          --------------------------
this Agreement, under no circumstances shall a Party hereto, as a result of this
Agreement, obtain any ownership interest in or other right to any technology,
know-how, patents, pending patent applications, products, or biological
materials of the other Party, including items owned, controlled or developed by
the other party, or transferred by the other Party to said Party at any time
pursuant to this Agreement.  It is understood and agreed that, except as
expressly set forth herein, this Agreement does not grant (i) Shire any license
or other right in the Cortex Patent Rights, Cortex Technology or Cortex
Inventions, or Cortex's interest in Joint Inventions and Joint Patent Rights
outside the Field, and (ii) Cortex any license or other right in the Shire
Inventions, or Shire's interest in Joint Inventions and Joint Patent Rights.

     9.4  Enforcement of Patent Rights.  Cortex and Shire shall each promptly
          ----------------------------
notify the other in writing of any actual alleged or threatened infringement of
patents or patent applications included in the Cortex Patent Rights, Cortex
Inventions, Joint Inventions or Joint Patents licensed hereunder of which they
become aware.  Cortex and Shire shall then confer and endeavor to reach
agreement of how to prevent, end or prosecute any such infringement.  If the
Parties do not agree on whether or how to proceed with enforcement activity
within (i) thirty (30) days following the notice of alleged infringement or (ii)
ten (10) business days before the time limit, if any, set forth in the
appropriate laws and regulations for the filing of such actions, whichever comes
first, then Cortex may commence litigation within an additional thirty (30) day
period with respect to the alleged or threatened infringement at its own
expense.  In the event that Cortex does not commence litigation, Shire may do so
and credit against royalties otherwise due Cortex under Section 7.5, with
respect to Net Sales in the country or countries in which such litigation is
undertaken, all of its reasonable expenses incurred in such action (including
attorneys' fees and expenses).  In the event a Party brings an infringement
action, the other Party shall cooperate fully, including, if required to bring
such action, the furnishing of a power of attorney.  Neither Party shall have
the right to settle any patent infringement litigation under this Section in a
manner that diminishes the rights or interests of the other Party without the
express written consent of such other Party, such consent not to be unreasonably
withheld or delayed.

          Except as otherwise agreed to by the Parties as part of a cost sharing
arrangement, any recovery realized as a result of such litigation shall be first
allocated to the Party or Parties in proportion to their expenses (taking into
account any crediting of royalties by Shire as permitted above) and then shall
be shared in the same ratio as the profits received by Shire or its Affiliates
in connection with sales of Products in such country has to the royalties paid
to Cortex in connection with the sale of Products in such country.

                                      17
<PAGE>

     9.5  Infringement of Third Party Patent Rights.
          -----------------------------------------

          9.5.1  Joint Strategy.  In the event that the manufacture, use or sale
                 --------------
of a Product licensed hereunder amounts to or becomes the subject of a claim of
infringement of a patent, copyright or other proprietary right anywhere in the
world, and without regard to which Party is charged with said infringement, and
the venue of such claim, the Parties shall promptly confer to discuss
appropriate steps to be taken to enable Shire to exercise its rights pursuant to
the licenses granted under this Agreement, including whether and how to contest
any claim.

          9.5.2  Defense.  If within thirty (30) days, the Parties fail to agree
                 -------
on a course of action, Shire may in good faith take such action as it sees fit
in order to continue development or commercialize the Product, including the
defense of any claim or the negotiation of a Third Party license, in which case
Shire shall keep Cortex reasonably informed of its progress.  Settlement of any
such Third Party claim or any such Third Party license shall not be concluded
without the prior consent of Cortex, which shall not be unreasonably withheld or
delayed.  Shire shall be entitled, in respect to the countries affected by such
Third Party rights to apply royalties otherwise payable to Cortex under this
Agreement with respect to such countries against Shire's reasonable legal and
expert fees in defending such claim and any damages awarded against it, provided
that the royalties payable to Cortex with respect to such country shall not be
reduced by more than fifty percent (50%) in any Quarter.

10.  CONFIDENTIALITY

     10.1 Nondisclosure Obligations.  Except as otherwise provided in this
          -------------------------
Article 10, during the term of this Agreement and for a period of ten (10) years
thereafter, both Parties shall maintain in confidence and use only for purposes
specifically authorized under this Agreement information and data received from
the other Party in connection with this Agreement or developed during the
Research Phase or Development Phase ("Information").

          To the extent it is reasonably necessary or appropriate to fulfill its
obligations or exercise its rights under this Agreement, a Party may disclose
Information it is otherwise obligated under this Section not to disclose to its
Affiliates, sublicensees, consultants, professional advisors, outside
contractors and clinical investigators, on a need-to-know basis on condition
that such entities or persons agree to confidentiality and non-use provisions in
relation to the Information on such terms as the disclosing Party uses for its
own confidential information of similar commercial importance; and a Party, its
Affiliate or its sublicensees may disclose such Information to government or
other regulatory authorities to the extent that such disclosure is required by
law or regulation or is reasonably necessary to obtain patents or authorizations
to conduct clinical trials with and to commercially market any Product.  The
obligation not to disclose Information shall not apply to any part of such
Information that (i) is or becomes patented, or published or (ii) is or becomes
part of the public domain other than by acts of the Party obligated not to
disclose such Information or its Affiliates or sublicensees in contravention of
this Agreement; (iii) is disclosed to the receiving Party or its Affiliates or
sublicensees by a Third Party, provided such Information was not knowingly
obtained by such Third Party directly or indirectly from the other Party under
this Agreement; (iv) prior to disclosure under this Agreement, was already in
the possession of the receiving Party or its Affiliates or sublicensees,
provided such Information was not knowingly obtained directly or indirectly from
the other Party under this Agreement; or (v) can be shown by written documents
to have been independently developed by the receiving Party or its Affiliates or
sublicensees without the aid or reference to the Information.

                                      18
<PAGE>

     10.2 Terms of this Agreement.  Cortex and Shire each agrees not to disclose
          -----------------------
any terms or conditions of this Agreement to any Third Party without the prior
consent of the other Party, except as required by applicable law or to persons
with whom Shire or Cortex has entered into or proposes to enter into a business
relationship provided that such persons are subject to appropriate
confidentiality agreements.  If a Party is required by law or regulation to
disclose Information to its government or other regulatory authorities, that
Party shall make reasonable efforts to keep the Information confidential and
protected from public disclosure.

11.  PUBLICITY AND PUBLICATIONS

     11.1 Publications.  In the event that either Party wishes to make a
          ------------
publication (which term shall include any oral disclosure to be made without
obligation of confidentiality) relating to any results obtained pursuant to or
in connection with this Agreement (the "Publishing Party"), it shall submit to
the other Party a copy of the proposed publication at least forty-five (45) days
prior to the intended date of submission for publication (or, in the case of an
oral disclosure, a written abstract thereof at least fifteen (15) days prior to
the date of intended disclosure), and

          11.1.1  subject to Section 11.1.2 below, if the Publishing Party is
Cortex, Shire shall have the right to delay or prevent publication as it sees
fit; or

          11.1.2  if the Publishing Party is Shire, or is Cortex (but only where
Cortex is subject to a Third Party obligation to seek to publish, evidence of
which shall be provided on Shire's request), the other Party shall be entitled
to propose modifications or request a delay in publication of up to forty-five
(45) days in order to obtain relevant patent protection.  Following
consideration of the other Party's comments or expiry of the forty-five (45) day
period (as appropriate), the Publishing Party shall be free to publish.

     11.2 Press Release.  The Parties shall issue a press release on execution
          -------------
of this Agreement, and subsequent press releases shall be issued in accordance
with this Section.  Shire shall submit a draft to Cortex in sufficient time to
enable Cortex to consider and comment thereon and the Parties shall co-operate
in good faith as to the form, content and timing of any announcement.  Neither
Party shall make any public announcement relating to the terms of this
Agreement, its subject matter or performance under it, to the extent not
previously publicly disclosed, without the prior written consent of the other
Party (which shall not be unreasonably withheld or delayed) except such as may
be required by law or the rules any stock exchange, in which case the other
Party will be given as much notice as is reasonably practicable in order to
allow such Party to comment thereon.

12.  REPRESENTATIONS AND WARRANTIES

     12.1 Authorization.  Each Party represents and warrants to the other that
          -------------
it has the legal right and power to enter into this Agreement, to extend the
rights and licenses granted or to be granted to the other in this Agreement, and
to fully perform its obligations hereunder, and that it has not made nor will it
make any commitments to others in conflict with or in derogation of such rights
or this Agreement.  Except as otherwise disclosed, each Party further represents
to the other that it is not aware of any legal obstacles, including, patent
rights of others, which could prevent it from carrying out its obligations under
this Agreement.

                                      19
<PAGE>

     12.2 Cortex Intellectual Property Representations and Warranties.
          -----------------------------------------------------------

          12.2.1  Patent Rights.  Cortex represents and warrants that it is the
                  -------------
sole and exclusive owner or exclusive licensee of the entire right, title and
interest in and to the Cortex Patent Rights and the Cortex Technology and that
it has the right to license the same to Shire under this Agreement.  Cortex
represents and warrants that, as of the Effective Date, the Cortex Patent Rights
and the Cortex Technology are free of any encumbrances, including, without
limitation, liens, licenses, judgments and/or security interests in the Field,
and that all patents and patent applications included in the Cortex Patent
Rights are in full force and effect as of the date hereof of this Agreement and
that none of the Cortex Patent Rights are the current subject of any
interference or opposition proceeding.

          12.2.2  Litigation.  Cortex represents and warrants that as of the
                  ----------
Effective Date there is no pending, or to its knowledge threatened, litigation
that would or might adversely affect its right and ability to grant the licenses
and to perform its obligations, or Shire's ability to exercise its rights, under
this Agreement.

          12.2.3  Validity and Infringement.  Cortex makes no representation or
                  -------------------------
warranty as to the validity of any of its patents and applications which are
included in the Cortex Patent Rights, or as to the non-infringement of any Third
Party patent(s) by the manufacture, use or sale of compounds or products or the
practice of any processes or methods covered by the Cortex Patent Rights by
Cortex, its Affiliates or licensees.  However, Cortex does represent and warrant
that to the best of its knowledge as of the date hereof: (i) it is unaware of
any publications or activities--including, without limitation, patents,
articles, and public uses or sales, by it or others, which would or might
invalidate any claim(s) of any patent or patent application included in the
Cortex Patent Rights, (ii) it has not conducted, or has not commissioned the
conducting of or received reports of, any formal or informal infringement or
validity studies regarding any patent or patent application included in the
Cortex Patent Rights that it has not fully disclosed in writing to Shire prior
to the date hereof; (iii) it has disclosed to Shire any Third Party patent(s) of
which it is aware that might be infringed by the manufacture, use or sale of any
compounds or products or the practice of any methods or processes by Shire, its
Affiliates or sublicensees of the Cortex Patent Rights, (iv) it is not aware of
any claim or accusation (whether outstanding or resolved) that any compounds or
products manufactured, used or sold by Cortex or any methods or process
practiced by Cortex which are included in the rights granted to Shire in this
Agreement or will be used by Cortex on carrying out its obligations under this
Agreement infringes or may infringe any Third Party patent(s), or other right,
and (v) it does not own or license any patents or patent applications not
included in the Cortex Patent Rights which would be infringed by the
manufacture, use or sale of any compounds or products or the practice of any
methods or processes covered by the Cortex Patent Rights or included in the
Cortex Technology by Shire, its Affiliates or sublicensees.

          12.2.4  Disclosure.  Cortex represents and warrants that it has and
                  ----------
will disclose to Shire all of the Cortex Technology.

          12.2.5  Maintenance of Confidential Information.  Cortex represents
                  ---------------------------------------
and warrants that it has taken all reasonable and necessary steps to protect the
Cortex confidential Information contained in the Cortex Patents and Cortex
Technology.

                                      20
<PAGE>

     12.3 Cortex License Representation and Warranties.
          --------------------------------------------

          12.3.1  License Agreements.  Cortex represents and warrants that as of
                  ------------------
the Effective Date all licenses with Third Parties for Cortex Patent Rights or
Cortex Technology are set forth on Exhibit F ("Third Party Licenses"), and that
                                   ---------
copies of such Third Party Licenses have been provided to Shire.

          12.3.2  Effectiveness, Maintenance.  As of the Effective Date,  Cortex
                  --------------------------
represents and warrants that all such Third Party Licenses are in full force and
effect and neither Cortex, or to Cortex's knowledge, the other party, is in
breach thereof.  Cortex shall maintain and procure the maintenance of all such
Third Party Licenses in full force and effect during the term of this Agreement
as is necessary to provide Shire the rights initially granted and to be granted
hereunder, including, without limitation, fulfilling all its obligations
thereunder and refraining from any acts which may give rise to a termination of
any Third Party License.

          12.3.3  Exclusivity. Cortex represents and warrants that all such
                  -----------
Third Party Licenses identified on Exhibit F as exclusive are exclusive to
                                   ---------
Cortex as is necessary to provide Shire the exclusive licenses provide herein
and, pursuant to the terms thereof, no such Third Party licensor of Cortex has
the right to grant licenses in the Field of patents or technology contained in
the Cortex Patent Rights and Cortex Technology or in the Joint Inventions and
Joint Patent Rights.

13.  INDEMNITY

     13.1 Shire Indemnity Obligations.  In the absence of Cortex's negligence, a
          ---------------------------
breach of contract or warranty by Cortex or willful or tortious acts or
omissions of Cortex, Shire agrees to defend, indemnify and hold Cortex, its
Affiliates and their respective employees and agents harmless from all Third
Party claims, losses, damages or expenses, but excluding consequential losses,
including, without limitation, economic loss or loss of profit, arising as a
result of: (a) actual or asserted violations of any applicable law or regulation
by Shire, its Affiliates or sublicensees by virtue of which Products
manufactured, distributed or sold by Shire, its Affiliates or sublicensees shall
be alleged or determined to be adulterated, misbranded, mislabeled or otherwise
not in compliance with any applicable law or regulation; (b) claims for bodily
injury, death or property damage attributable to the development, manufacture,
distribution, sale or use of Products by Shire, its Affiliates or sublicensees;
(c) a recall of Products manufactured, distributed or sold by Shire, its
Affiliates or sublicensees ordered by a governmental agency or required by a
confirmed Product failure as reasonably determined by Shire; (d) the negligent,
willful or tortious acts or omissions of Shire, its Affiliates and sublicensees
and their respective employees and agents in connection with the development,
use, sale or supply of the Product; or (e) any breach of Shire's representations
and warranties herein or other breach of the terms of this Agreement.

     13.2 Cortex Indemnity Obligations.  Cortex agrees to defend, indemnify and
          ----------------------------
hold Shire, its Affiliates and their respective employees and agents harmless
from all Third Party claims, losses, damages or expenses but excluding
consequential losses, including, without limitation, economic loss or loss of
profit arising as a result of: (a) the negligent, willful or tortious acts or
omissions of Cortex, its Affiliates and their respective employees and agents;
or (b) any breach of Cortex's representations and warranties herein or other
breach of the terms of this Agreement.

     13.3 Procedure.  A Party or any of its Affiliates or their respective
          ---------
employees or agents (the "Indemnitee") that intends to claim indemnification
under this Article 13 shall promptly notify

                                      21
<PAGE>

the other Party (the "Indemnitor") of any loss, claim, damage, liability or
action in respect of which the Indemnitee intends to claim such indemnification,
and the Indemnitor shall assume the defense thereof with counsel mutually
satisfactory to the Parties; provided, however, that an Indemnitee shall have
the right to retain its own counsel, with the fees and expenses to be paid by
the Indemnitor, if representation of such Indemnitee by the counsel retained by
the Indemnitor would be inappropriate due to actual or potential conflicting
interests between such Indemnitee and any other Party represented by such
counsel in such proceedings. The indemnity agreement in this Article 13 shall
not apply to amounts paid in settlement of any loss, claim, damage, liability or
action if such settlement is effected without the consent of the Indemnitor,
which consent shall not be withheld unreasonably. The failure to deliver notice
to the Indemnitor within a reasonable time after the commencement of any such
action, if materially prejudicial to its ability to defend such action, shall
relieve such Indemnitor of any liability to the Indemnitee under this Article
13, but the omission so to deliver notice to the Indemnitor will not relieve it
of any liability that it may have to any Indemnitee otherwise than under this
Article 13. The Indemnitee under this Article 13, its employees and agents,
shall cooperate fully with the Indemnitor and its legal representatives in the
investigation of any action, claim or liability covered by this indemnification.
In the event that either Party claims indemnity from the other and one Party is
finally held liable to indemnify the other, the Indemnitor shall additionally be
liable to pay the reasonable legal costs and attorneys' fees incurred by the
Indemnitee in establishing its claim for indemnity.

     13.4 Warranty Limitation.  EXCEPT AS EXPRESSLY STATED IN THIS AGREEMENT,
          -------------------
NEITHER PARTY MAKES ANY WARRANTY, AND EACH PARTY EXPRESSLY DISCLAIMS ALL
DISCLAIMS, ALL IMPLIED WARRANTIES, INCLUDING WARRANTIES OR MERCHANTABILITY OR
FITNESS FOR A PARTICULAR PURPOSE, WITH RESPECT TO ANY COMPOUNDS OR OTHER
BIOLOGICAL OR CHEMICAL MATERIALS OR INFORMATION PROVIDED TO THE OTHER PARTY
PURSUANT TO THIS AGREEMENT.

     13.5 Insurance.  Shire shall maintain comprehensive general liability
          ---------
insurance against claims regarding the implementation and execution of this
Agreement, including but not limited to the development, manufacture and sale of
Products, in such amounts as Shire customarily maintains with similar
activities.  Shire shall maintain such insurance during the term of this
Agreement and thereafter for so long as it continues to manufacture or sell any
Products.  Shire shall provide Cortex proof of such insurance upon request.
Shire shall give Cortex at least thirty (30) days notice of any cancellation,
termination or change in such instance.

14.  TERM AND TERMINATION

     14.1 Expiration of This Agreement.  Unless terminated earlier pursuant to
          ----------------------------
Section 14.2, this Agreement shall expire and the licenses granted by Cortex to
Shire shall become fully paid and irrevocable on a country-by-country basis upon
the later of (i) ten (10) years after the First Commercial Sale of the Products
in such country or (ii) the expiration of any patents included in the Cortex
Patent Rights (including Cortex interest in Joint Patent Rights).

     14.2 Termination of This Agreement.  This Agreement may be terminated in
          -----------------------------
the following circumstances:

          14.2.1  Material Breach.  By one Party upon written notice by reason
                  ---------------
of a material breach by the other Party that the breaching Party fails to remedy
within ninety (90) days after

                                      22
<PAGE>

written notice thereof by the non-breaching Party, provided however, that in the
case that such breach is capable of cure but cannot be cured within such ninety
(90) day period, such period shall be extended so long as the breaching Party
continues to use diligent efforts to cure such breach;

          14.2.2  Failure of Shire to Pay.  By Cortex, if Shire fails to make
                  -----------------------
(i) any payment under Article 7 within ten (10) days after notice from Cortex
that such payment is due and payable (unless there is a bona fide, good faith
dispute as to whether such payment is due and payable) or (ii) any royalty
payment under Section 7.5 within twenty (20) days after notice from Cortex that
such payment is due and payable (unless there is a bona fide, good faith dispute
as to whether such payment is due and payable);

          14.2.3  Bankruptcy.  By either Party upon bankruptcy, insolvency,
                  ----------
dissolution or winding up of the other;

          14.2.4  By Shire in Part.  By Shire, in its discretion, at any time
                  ----------------
after the expiration of the Research Phase on a country-by-country basis upon
delivery by Shire to Cortex of six (6) months prior notice thereof;

          14.2.5  By Shire in Whole.  By Shire, in its discretion, at any time
                  -----------------
after the expiration of the Research Phase, in its entirety, upon delivery by
Shire to Cortex of six (6) months prior notice thereof; or

          14.2.6  Failure to Meet Development Base Timeline.  By Cortex, if no
                  -----------------------------------------
Development Plan progresses in accordance with the Development Base Timeline in
the United States (subject to adjustment pursuant to Section 4.3), upon delivery
of written notice to Shire.

     14.3 Effect of Expiration or Termination of This Agreement Generally.
          ---------------------------------------------------------------

          14.3.1  Existing Obligations.  Expiration pursuant to Section 14.1 or
                  --------------------
termination pursuant to Section 14.2 of this Agreement for any reason shall not
relieve the Parties of any obligation that accrued prior to such expiration or
termination.

          14.3.2  Survival.  The provisions of Article 7 (with respect only to
                  --------
payments and royalties accrued at the time of expiration or termination but not
yet paid), Section 9.1, Article 10, Article 11, Article 12, Article 13 and this
Section 14.3.2 shall survive the expiration pursuant to Section 14.1 or
termination pursuant to Section 14.2 of this Agreement.

     14.4 Effect of Termination by Cortex.  In the event that this Agreement is
          -------------------------------
terminated by Cortex pursuant to Section 14.2.1, 14.2.2 or 14.2.3 or 14.2.6:

          14.4.1  Termination of Licenses.  All licenses and rights granted to
                  -----------------------
Shire hereunder shall terminate and, except as provided in Section 14.4.2.
below, Shire will immediately cease to manufacture and sell Products;

          14.4.2  Disposition of Inventory of Products.  (a) Shire may dispose
                  ------------------------------------
of its inventory of Products on hand as of the effective date of termination,
and may fill any orders for Products accepted prior to the effective date of
termination, for a period of twelve (12) months after the effective date of
termination and (b) within thirty (30) days after disposition of such inventory
and fulfillment of such orders (and in any event within seven (7) months after
termination) Shire will

                                      23
<PAGE>

forward to Cortex a final report containing the details required by Section 7.5
hereof and pay Cortex all royalties due for Net Sales in such period; and

          14.4.3    Shire Data.  Shire shall grant Cortex a perpetual, non-
                    ----------
exclusive, fully-paid and royalty-free right and license to use in the
manufacture and commercialization of the Products any Shire Data.

     14.5 Effect of Termination in Full or in Part by Shire.  In the event that
          -------------------------------------------------
Shire terminates, in full or in part, this Agreement pursuant to Sections 14.2.1
or 14.2.3, the applicable licenses and rights granted to Shire shall terminate
and Shire will immediately cease to manufacture and sell Products except as
provided in this Section 14.5 and Shire shall be entitled to claim from Cortex
all damages which would otherwise be due to Shire under law and equity.  If
Shire so elects to terminate this Agreement, then (a) Shire may dispose of its
inventory of Products on hand as of the effective date of termination, and may
fill any orders for Products accepted prior to the effective date of
termination, for a period of twelve (12) months after the effective date of
termination and (b) within thirty (30) days after disposition of such inventory
and fulfillment of such orders (and in any event within seven (7) months after
termination) Shire will forward to Cortex a final report containing the details
required by Section 7.5 hereof and pay Cortex all royalties due for Net Sales in
such period.

     14.6 Additional Rights to Shire in the Event of Cortex Bankruptcy.  All
          ------------------------------------------------------------
licenses granted under this Agreement are deemed to be, for purposes of Section
365(n) of the U.S. Bankruptcy Code, licenses of right to "intellectual property"
as defined in Section 101 of such Code.  The Parties agree that Shire may fully
exercise all of its rights and elections under the Bankruptcy Code.  The Parties
further agree that, in the event Shire elects to retain its rights as a licensee
under such Code, Shire shall be entitled to complete access to the Cortex
Technology and Patents licensed to it hereunder and all embodiments of such
Cortex Technology and Patents, for the purposes of exploitation of the licenses
granted under this Agreement.  Such embodiments of the Cortex Technology and
Patents shall be delivered to Shire not later than:

          14.6.1.1  the commencement of bankruptcy proceedings against
Cortex, upon written request, unless Cortex elects to perform its obligations
under the Agreement, or

          14.6.1.2  if not delivered under (a) above, upon the rejection of this
Agreement by or on behalf of the Cortex, upon written request.

15.  MISCELLANEOUS

     15.1 Force Majeure.  Neither Party shall be held liable or responsible to
          -------------
the other Party nor be deemed to have defaulted under or breached this Agreement
for failure or delay in fulfilling or performing any term of this Agreement when
such failure or delay is caused by or results from causes beyond the reasonable
control of the affected Party, including but not limited to fire, floods,
embargoes, war, acts of war (whether war is declared or not), insurrections,
riots, civil commotions, strikes, lockouts or other labor disturbances, acts of
God or acts, omissions or delays in acting by any governmental authority or the
other Party; provided, however, that the Party so affected shall use reasonable
commercial efforts to avoid or remove such causes of nonperformance, and shall
continue to perform hereunder with reasonable dispatch whenever such causes are
removed.  Either Party shall provide the other Party with prompt written notice
of any delay or failure to perform that occurs by reason of force majeure.  The
Parties shall mutually seek a resolution of the delay or the failure to perform
as noted above.

                                      24
<PAGE>

     15.2  Assignment.  This Agreement may not be assigned or otherwise
           ----------
transferred by either Party without the prior written consent of the other
Party, which consent shall not be unreasonably withheld or delayed; provided,
however, that each of the Parties may, without such consent, assign this
Agreement and its rights and obligations hereunder to its Affiliates or in
connection with the transfer or sale of all or substantially all of its
business, or in the event of its merger or consolidation or change in control or
similar transaction (which shall be deemed an assignment).  Any purported
assignment in violation of the preceding sentences shall be void.  Any permitted
assignee shall assume all obligations of its assignor under this Agreement in
writing.

     15.3  Severability.  Each Party hereby agrees that it does not intend to
           ------------
violate any public policy, statutory or common laws, rules, regulations, treaty
or decision of any government agency or executive body thereof of any country or
community or association of countries.  Should one or more provisions of this
Agreement be or become invalid, the Parties hereto shall substitute, by mutual
consent, valid provisions for such invalid provisions which valid provisions in
their economic effect are sufficiently similar to the invalid provisions that it
can be reasonably assumed that the Parties would have entered into this
Agreement with such valid provisions.  In case such valid provisions cannot be
agreed upon, the invalidity of one or several provisions of this Agreement shall
not affect the validity of this Agreement as a whole, unless the invalid
provisions are of such essential importance to this Agreement that it is to be
reasonably assumed that the Parties would not have entered into this Agreement
without the invalid provisions.

     15.4  Notices.  Any consent, notice or report required or permitted to be
           -------
given or made under this Agreement by one of the Parties hereto to the other
shall be in writing, delivered personally or by facsimile (and promptly
confirmed by personal delivery or courier) or courier, postage prepaid (where
applicable), addressed to such other Party at its address indicated below, or to
such other address as the addressee shall have last furnished in writing to the
addressor and shall be effective upon receipt by the addressee.

     If to Cortex:       Cortex Pharmaceuticals, Inc.
                         15241 Barranca Parkway
                         Irvine, California 92618-2201
                         Attention: Chief Executive Officer
                         Fax: 949/727-3657

     with a copy to:     Stradling Yocca Carlson & Rauth
                         660 Newport Center Drive, Suite 1600
                         Newport Beach, California 92660
                         Attention: Lawrence B. Cohn
                         Fax: 949/725-4100

     If to Shire:        Shire Holdings AG
                         Bundesstrasse 5, 6300 Zug, Switzerland
                         Attention: Company Secretary

     with a copy to:     Shire Pharmaceuticals Group plc
                         East Anton, Andover, Hampshire, SP10 5RG England
                         Attention: Company Secretary
                         Fax: (011) 44-1264-332-879

                                      25
<PAGE>

     15.5  Governing Law, Venue.  This Agreement shall be governed by, and
           --------------------
construed in accordance with, the laws of the State of California and the United
States, as though made and to be fully performed therein without regard to
conflicts of laws principles thereof.  Except as otherwise set forth below in
Section 15.6, all disputes with respect to this Agreement and the subject matter
hereof shall be heard exclusively in the state or federal courts in Orange
County, California, and the parties agree to the jurisdiction of such courts.

     15.6  Arbitration.  Any disputes arising between the Parties relating to,
           -----------
arising out of or in any way connected with this Agreement or any term or
condition hereof, or the performance by either Party of its obligations
hereunder, whether before or after termination of this Agreement, shall be
promptly presented to the Chief Executive Officers of Cortex and Shire for
resolution and if the Chief Executive Officers cannot promptly resolve such
disputes, then such dispute shall be finally resolved by binding arbitration.
Whenever a Party shall decide to institute arbitration proceedings, it shall
give written notice to that effect to the other Party.  The Party giving such
notice shall refrain from instituting the arbitration proceedings for a period
of sixty (60) days following such notice.  Any arbitration hereunder shall be
conducted under the Commercial Arbitration Rules of the American Arbitration
Association.  Each such arbitration shall be conducted by a panel of one or
three arbitrators appointed in accordance with such Rules.  Any such arbitration
shall be held in Orange County, California, United States of America.  The
arbitrators shall have the authority to grant specific performance, and to
allocate between the Parties the costs of arbitration in such equitable manner
as they determine.  Judgment upon the award so rendered may be entered in any
court having jurisdiction or application may be made to such court for judicial
acceptance of any award and an order of enforcement, as the case may be.

     15.7  Entire Agreement.  This Agreement, together with the Exhibits hereto,
           ----------------
the Option Agreement and the Stock Purchase Agreement between the Parties
contains the entire understanding of the Parties with respect to the subject
matter hereof.  In the event of any conflict or inconsistency between any
provision of any Exhibit hereto and any provision of this Agreement, the
provisions of this Agreement shall prevail.  All express or implied agreements
and understandings, either oral or written, heretofore made are expressly merged
in and made a part of this Agreement.  This Agreement may be amended, or any
term hereof modified, only by a written instrument duly executed by both Parties
hereto.

     15.8  Headings.  The captions to the several Articles and Sections hereof
           --------
and Exhibits hereto are not a part of this Agreement, but are merely guides or
labels to assist in locating and reading the several Articles and Sections
hereof.

     15.9  Independent Contractors.  It is expressly agreed that Cortex and
           -----------------------
Shire shall be independent contractors and that the relationship between the two
Parties shall not constitute a partnership, joint venture or agency.  Neither
Cortex nor Shire shall have the authority to make any statements,
representations or commitments of any kind, or to take any action, which shall
be binding on the other, without the prior consent of the other Party to do so.

     15.10 Waiver.  The waiver by either Party hereto of any right hereunder or
           ------
the failure to perform or of a breach by the other Party shall not be deemed a
waiver of any other right hereunder or of any other breach or failure by said
other Party whether of a similar nature or otherwise.

                                      26
<PAGE>

     15.11  Counterparts.  This Agreement may be executed in two or more
            ------------
counterparts, each of which shall be deemed an original, but all of which
together shall constitute one and the same instrument.

     IN WITNESS WHEREOF, the Parties have executed this Agreement as of the date
first set forth above.

                              CORTEX PHARMACEUTICALS, INC.

                              By: __________________________________

                              Name:_________________________________

                              Title:________________________________

                              SHIRE HOLDINGS AG

                              By:___________________________________

                              Name:_________________________________

                              Title:________________________________

                                      27
<PAGE>

                                 SCHEDULE 1.7
                                 ------------

                                      [*]


                SEVEN PAGES OF THIS SCHEDULE HAVE BEEN OMITTED

* CONFIDENTIAL PROVISIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION
<PAGE>

                                 SCHEDULE 1.10
                                 -------------

                                      [*]

                THREE PAGES OF THIS SCHEDULE HAVE BEEN OMITTED

   * CONFIDENTIAL PROVISIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION

                                       2
<PAGE>

                                 SCHEDULE 1.12
                                 -------------

                                      [*]

                  ONE PAGE OF THIS SCHEDULE HAS BEEN OMITTED

* CONFIDENTIAL PROVISIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION
<PAGE>

                                 SCHEDULE 1.29
                                 -------------

                     INVESTIGATIONAL NEW DRUG APPLICATION
                     ------------------------------------

(S) 312.21 Phases of an investigation.

     An IND may be submitted for one or more phases of an investigation.  The
clinical investigation of a previously untested drug is generally divided into
three phases.  Although in general the phases are conducted sequentially, they
may overlap.  These three phases of an investigation are as follows:

     (a)  Phase 1.  Phase 1 includes the initial introduction of an
          -------
investigational new drug into humans.  Phase 1 studies are typically closely
monitored and may be conducted in patients or normal volunteer subjects.  These
studies are designed to determine the metabolism and pharmacologic actions of
the drug in humans, the side effects associated with increasing doses, and, if
possible, to gain early evidence on effectiveness.  During Phase 1, sufficient
information about the drug's pharmacokinetics and pharmacological effects should
be obtained to permit the design of well-controlled, scientifically valid, Phase
2 studies.  The total number of subjects and patients included in Phase 1
studies varies with the drug, but is generally in the range of 20 to 80.

     Phase 1 studies also include studies of drug metabolism, structure-activity
relationships, and mechanism of action in humans, as well as studies in which
investigational drugs are used as research tools to explore biological phenomena
or disease processes.

     (b)  Phase 2.  Phase 2 includes the controlled clinical studies conducted
          -------
to evaluate the effectiveness of the drug for a particular indication or
indications in patients with the disease or condition under study and to
determine the common short-term side effects and risks associated with the drug.
Phase 2 studies are typically well controlled, closely monitored, and conducted
in a relatively small number of patients, usually involving no more than several
hundred subjects.

     (c)  Phase 3.  Phase 3 studies are expanded controlled and uncontrolled
          -------
trials.  They are performed after preliminary evidence suggesting effectiveness
of the drug has been obtained, and are intended to gather the additional
information about effectiveness and safety that is needed to evaluate the
overall benefit-risk relationship of the drug and to provide an adequate basis
for physician labeling.  Phase 3 studies usually include from several hundred to
several thousand subjects.

                                       2
<PAGE>

                                 SCHEDULE 1.35
                                 -------------

                                 RESEARCH PLAN
<PAGE>

                                                                  EXECUTION COPY
                                                                  April 19, 2000

                         CONFIDENTIAL PORTIONS OMITTED
                         -----------------------------


                                   EXHIBIT B

                           STOCK PURCHASE AGREEMENT

                                    between

                         CORTEX PHARMACEUTICALS, INC.

                                      and

                       SHIRE PHARMACEUTICALS GROUP, plc

                          dated as of April 19, 2000



                              (Option Agreement)
<PAGE>

                           STOCK PURCHASE AGREEMENT

          THIS STOCK PURCHASE AGREEMENT (the "Agreement") dated as of April 19,
2000 (the "Effective Date") is made between CORTEX PHARMACEUTICALS, INC., having
its principal offices at 15241 Barranca Parkway, Irvine, California ("Cortex")
U.S.A., and Shire Pharmaceuticals Group, plc., having its principal offices at
East Anton, Andover, Hampshire, SP10 5RG England ("Shire"). All terms not
otherwise defined herein are defined in either the Option Agreement or the
Development and License Agreement described below. The execution and delivery of
this Agreement shall constitute the "Closing".

                                R E C I T A L S

          A. Cortex possesses know-how, expertise and rights to issued United
States patents and patent applications with corresponding foreign filed patent
applications pertaining to a class of proprietary pharmaceuticals called
AMPAKINES(R).

          B. Cortex and Shire have on even date herewith entered into an Option
Agreement (the "Option Agreement"). In connection with the Option Agreement,
Shire shall purchase Common Stock of Cortex on the terms and conditions set
forth herein.

          NOW THEREFORE, in consideration of the premises and of the covenants
herein contained, the parties hereto mutually agree as follows:

                       ARTICLE 1:  SALE OF CORTEX SHARES

          1.1  Sale of Common Stock.  Subject to the satisfaction of the terms
               --------------------
and conditions of the Closing set forth herein and in reliance upon the
respective representations and warranties of the parties set forth herein or in
any document delivered pursuant hereto, Cortex agrees to sell to Shire upon the
Closing a number of shares of Cortex Common Stock = $870,000/FMV, where FMV
equals the average of the closing sales price of Cortex Common Stock, as
reported on the NASDAQ OTC Bulletin Board, on the [*] trading days consisting of
the [*] trading days immediately preceding the Effective Date, and the [*]
trading days immediately following the Effective Date. The aggregate purchase
price of the shares shall be $870,000 . The shares of Common Stock which are to
be purchased pursuant to this Article referred to herein as the "Shares".

          1.2  Delivery of the Shares at the Closing. The Closing for the
               -------------------------------------
purchase of the shares shall occur on April 28, 2000 at a place and time (the
"Closing Date") to be agreed upon by Cortex and Shire. At the Closing, Shire
shall pay to Cortex the aggregate purchase price for the Shares being purchased
hereunder and Cortex shall deliver to Shire one or more stock certificates
registered in the name of Shire, or in such nominee name(s) as designated in
writing by Shire, representing the number of Shares being purchased. Cortex's
obligation to complete the purchase and sale of the Shares and deliver such
stock certificate(s) to Shire at the Closing shall be subject to the following
conditions, any one or more of which may be waived by Cortex: (a) receipt by
Cortex of a certified or bank check or wire transfer in the full amount of the
purchase price for the Shares being purchased hereunder and (b) the accuracy in
all material respects of the representations and warranties made by


* CONFIDENTIAL PROVISIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION

                                       1
<PAGE>

Shire herein and the fulfillment in all material respects of those undertakings
of Shire to be fulfilled prior to the Closing. Shire's obligation to accept
delivery of such stock certificate(s) and to pay for the Shares evidenced
thereby shall be subject to the accuracy in all material respects of the
representations and warranties made by Cortex herein and the fulfillment in all
material respects of those undertakings of Cortex to be fulfilled prior to the
Effective Date, any one or more of which conditions may be waived by Shire.

                   ARTICLE 2:  REPRESENTATIONS AND WARRANTIES

          2.1  Representations, Warranties and Covenants of Cortex.  Cortex
               ---------------------------------------------------
hereby represents and warrants to, and covenants with, Shire as follows:

               2.1.1  Organization and Qualification.  Cortex is a corporation
                      ------------------------------
duly organized, validly existing and in good standing under the laws of the
State of Delaware and has all requisite corporate power and authority to conduct
its business as currently conducted.

               2.1.2  Due Execution, Delivery and Performance of the Agreement.
                      --------------------------------------------------------
Cortex's execution, delivery and performance of this Agreement (a) has been duly
authorized under Delaware law by all requisite corporate action by Cortex, and
(b) will not violate any law or the Certificate of Incorporation or Bylaws of
Cortex or any subsidiary or any provision of any material indenture, mortgage,
agreement, contract or other material instrument to which Cortex or any
subsidiary is a party or by which Cortex or any of their respective properties
or assets is bound as of the date hereof, or result in a breach of or constitute
(upon notice or lapse of time or both) a default under any such indenture,
mortgage, agreement, contract or other material instrument or result in the
creation or imposition of any lien, security interest, mortgage, pledge, charge
or other encumbrance, of any material nature whatsoever, upon any properties or
assets of Cortex or any subsidiary. Upon its execution and delivery, and
assuming the valid execution thereof by Shire, the Agreement will constitute a
valid and binding obligation of Cortex, enforceable against Cortex in accordance
with its terms, except as enforceability may be limited by applicable
bankruptcy, insolvency, reorganization, moratorium or similar laws affecting
creditors' and contracting parties' rights generally and except as
enforceability may be subject to general principles of equity (regardless of
whether such enforceability is considered in a proceeding in equity or at law).

               2.1.3  Issuance, Sale and Delivery of the Shares. The shares
                      -----------------------------------------
have been duly authorized and reserved for issuance to Shire by all necessary
corporate action. When issued and paid for, the Shares to be sold hereunder by
Cortex will be validly issued and outstanding, fully paid and non-assessable.

               2.1.4  Additional Information.  Cortex represents and warrants
                      ----------------------
that all reports filed by Cortex with the Securities and Exchange Commission
(the "Commission") since January 1, 1998 pursuant to the reporting requirements
of the Securities Exchange Act of 1934, as amended (the "Exchange Act"), when
filed, did not contain any untrue statement of a material fact or omit to state
any material fact required to be stated therein or necessary to make the
statements therein, in light of the circumstances in which they were made, not
misleading.

               2.1.5  No Material Changes.  As of the date hereof, there has
                      -------------------
been no material adverse change in the financial condition or results of
operations of Cortex since the filing date of Cortex's last report with the
Commission pursuant to the reporting requirements of the Exchange Act.

                                       2
<PAGE>

     2.2  Representations, Warranties and Covenants of Shire.
          --------------------------------------------------

          2.2.1  Investment Considerations.  Shire represents and warrants to,
                 -------------------------
and covenants with, Cortex that:

                 (a) Shire has the business experience to protect its interests
in connection with this investment and has requested, received, reviewed and
considered all information it deems relevant in making an informed decision to
purchase the Shares;

                 (b) Shire is acquiring the Shares for its own account for
investment only and with no present intention of distributing any of such Shares
within the meaning of Section 2(11) of the Securities Act of 1933 (the
"Securities Act") or any arrangement or understanding with any other persons
regarding the distribution of such Shares (within the meaning of the Securities
Act);

                 (c) Shire understands that the Shares it is purchasing are
"restricted securities" under the federal securities laws inasmuch as they are
being acquired from Cortex in a transaction not involving a public offering and
that under such laws and applicable regulations such securities may be resold
without registration under the Securities Act only in certain limited
circumstances;

                 (d) Shire will not, directly or indirectly, offer, sell, pledge
transfer or otherwise dispose of (or solicit any offers to buy, purchase or
otherwise acquire or take a pledge of) any of the Shares except in compliance
with the Securities Act and the rules and regulations promulgated thereunder.
Without in any way limiting the representations set forth above, Shire further
agrees not to make any disposition of all or any portion of the Shares for a
period of the longer of (i) two (2) years following the date of acquisition of
the Shares, or (ii) if Shire exercises the Option under the Option Agreement,
the end of the Research Phase as defined in the Development and License
Agreement entered into between Shire and Cortex in connection with such Option
exercise, and, after such time, only if (x) there is then in effect a
Registration Statement under the Securities Act covering such proposed
disposition and such disposition is made in accordance with such Registration
Statement; or (y) (A) Shire shall have notified Cortex of the proposed
disposition and shall have furnished Cortex with a detailed statement of the
circumstances surrounding the proposed disposition, and (B) if requested by
Cortex, Shire shall have furnished Cortex with an opinion of counsel, reasonably
satisfactory to Cortex and its counsel, that such disposition will not require
registration of such shares under the Securities Act, provided that Cortex shall
not require such opinion to the extent such disposition is in accordance with
Rule 144. In addition, Shire will not dispose of more than [*] Shares in any
calendar month, irrespective of its disposition of shares in any prior calendar
month.

                 (e) Shire qualifies as an "accredited investor" within the
meaning of Rule 501 of Regulation D promulgated under the Securities Act; and

                 (f) It is understood that the certificates evidencing the
Shares shall bear the following legend:


* CONFIDENTIAL PROVISIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION

                                       3
<PAGE>

          "These securities have not been registered under the
           Securities Act of 1933. They may not be sold, offered for
           sale, pledged or hypothecated in the absence of a
           registration statement in effect with respect to the
           securities under such Act or, if requested by Cortex, an
           opinion of counsel reasonably satisfactory to Cortex and
           its counsel, that such registration is not required under
           such Act."


          2.2.2  Due Execution, Delivery and Performance of the Agreement.
                 --------------------------------------------------------
Shire further represents and warrants to, and covenants with, Cortex that (a)
Shire is a public limited company duly organized, validly existing and in good
standing under the laws of England and Wales and has full right, power,
authority and capacity to enter into this Agreement and to consummate the
transactions contemplated hereby and has taken all necessary action to authorize
the execution, delivery and performance of this Agreement, (b) the execution,
delivery and performance of this Agreement will not violate any law or the
Articles of Association of Shire or any subsidiary or any provision of any
material indenture, mortgage, agreement, contract or other material instrument
to which Shire or any subsidiary is a party or by which Shire, any subsidiary,
or any of their respective properties or assets is bound as of the date hereof,
or result in a breach of or constitute (upon notice or lapse of time or both) a
default under any such indenture, mortgage, agreement, contract or other
material instrument or result in the creation or imposition of any lien,
security interest, mortgage, pledge, charge or encumbrance, of any material
nature whatsoever, upon any assets of Shire or any subsidiary and (c) upon the
execution and delivery of this Agreement, this Agreement shall constitute a
valid and binding obligation of Shire enforceable in accordance with its terms,
except as enforceability may be limited by applicable bankruptcy, insolvency,
reorganization, moratorium or similar laws affecting creditors' and contracting
parties' rights generally and except as enforceability may be subject to general
principles of equity (regardless of whether such enforceability is considered in
a proceeding in equity or at law).

                        ARTICLE 3: REGISTRATION RIGHTS

     3.1  Registration Rights.  Cortex covenants and agrees as follows:
          -------------------

          3.1.1  Requested Registrations.  If Shire fails to exercise the
                 -----------------------
Option, then at any time after two (2) years following the Closing Date, or (ii)
if Shire does exercise the Option, then at any time after the end of the
Research Phase as defined in the Development and License Agreement, and subject
to the conditions herein set forth, Shire shall have the right to require Cortex
to effect the registration of Shares on a registration statement under the
Securities Act by giving Cortex written notice requesting such registration and
specifying the number of Shares proposed to be sold and the proposed plan for
distribution of such Shares; provided, however, that such request shall cover at
least [*] Shares. Shire shall be entitled to one requested registration on an
appropriate registration form for a registered offer. If and whenever Cortex
shall be required by the provisions of this Section 3.1.1 to effect the
registration of any Shares hereunder, Cortex will, as expeditiously as possible:

          (a)  use its best efforts to prepare and file a registration
statement, giving effect to the plan of distribution of the Shares proposed to
be sold, and use its best efforts to cause such registration statement to become
effective in order that Shire may sell its Shares in accordance with the
proposed plan of distribution;

* CONFIDENTIAL PROVISIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION

                                       4
<PAGE>

          (b)  prepare and file with the Commission such amendments and
supplements to such registration statement and the prospectus used in connection
therewith as may be necessary to keep such registration statement effective and
advise Shire promptly of any proposal to amend or supplement the registration
statement and to comply with the provisions of the Securities Act with respect
to the offer of the Shares covered by such registration statement during the
period required for distribution of the Shares, which period shall not be in
excess of nine (9) months from the effective date of such registration
statement;

          (c)  furnish Shire such number of copies of such prospectus as it may
reasonably request in order to facilitate the sale of the Shares;

          (d)  file documents required of Cortex for blue sky clearance in
states specified in writing by Shire; provided, however, that Cortex shall not
be required to qualify to do business or consent to service of process in any
jurisdiction in which it is now not so qualified or has not so consented; and

          (e)  use it best efforts to prevent the issuance of any stop order
with respect to any registration statement and, if any stop order is issued, to
obtain the lifting thereof at the earliest possible moment;

          (f)  file all documents required to be filed with the Commission
pursuant to the Exchange Act;

          (g)  have the Shares listed on the NASDAQ OTC Bulletin Board, or such
other exchange as the Common Stock may then be listed on;

          (h)  bear all expenses in connection with the procedures set forth in
paragraphs (a) through (d) of this Section 6.1 and the registration of the
Shares pursuant to the registration statement, other than fees and expenses, if
any, of counsel or other advisors to Shire.

     If at the time of any request to register Shares pursuant to this Section
6.1 Cortex is engaged or has fixed plans to engage within 60 days of the date of
receipt of the request in a registered public offering, or is engaged in any
other activity which, in the good faith determination of Cortex's Board of
Directors, would be adversely affected by the demand registration, then Cortex
may at its option direct that such request be delayed for a period not in excess
of 90 days from the closing of such offering or the date of Cortex's Board of
Directors' determination, as the case may be.

          3.1.2  Indemnification.  For the purpose of this Section 3.1.2,
                 ---------------

          (a)  the term "Selling Stockholder" shall mean Shire and any officer,
director, employee, agent, affiliate or person deemed to be in control of such
person within the meaning of Section 15 of the Securities Act or Section 20 of
the Exchange Act;

          (b)  the term "Registration Statement" shall mean any final
prospectus, exhibit, supplement or amendment included in or relating to the
registration statement referred to in Section 6.1; and

          (c)  the term "untrue statement" shall mean any untrue statement or
alleged untrue statement of, or any omission or alleged omission to state, in
the Registration

                                       5
<PAGE>

Statement a material fact required to be stated therein or necessary to make the
statements therein, in the light of the circumstances under which they were
made, not misleading.

     Cortex agrees to indemnify and hold harmless each Selling Stockholder from
and against any losses, claims, damages or liabilities to which such Selling
Stockholder may become subject (under the Securities Act or otherwise) insofar
as such losses, claims, damages or liabilities (or actions or proceedings in
respect thereof) arise out of, or are based upon, any untrue statement of a
material fact contained in the Registration Statement on or after the effective
date thereof, or arise out of any failure by Cortex to fulfill any undertaking
included in the Registration Statement and Cortex will reimburse such Selling
Stockholder for any reasonable legal or other expenses reasonably incurred in
investigating, defending or preparing to defend any such action, proceeding or
claim; provided, however, that Cortex shall not be liable in any such case to
the extent that such loss, claim, damage or liability arises out of, or is based
upon, an untrue statement made in such Registration Statement in reliance upon
and in conformity with written information furnished to Cortex by or on behalf
of such Selling Stockholder specifically for use in the Registration Statement,
or any statement or omission in any Prospectus that is corrected in any
subsequent Prospectus that was delivered to Shire prior to the pertinent sale or
sales by Shire.

     Shire agrees to indemnify and hold harmless Cortex (and each person, if
any, who controls Cortex within the meaning of Section 15 of the Securities Act,
each officer of Cortex who signs the Registration Statement and each director of
Cortex) from and against any losses, claims, damages or liabilities to which
Cortex (or any such officer, director or controlling person) may become subject
(under the Securities Act or otherwise), insofar as such losses, claims, damages
or liabilities (or actions or proceedings in respect thereof) arise out of, or
are based upon, any untrue statement of a material fact contained in the
Registration Statement on or after the effective date thereof if such untrue
statement was made in reliance upon and in conformity with written information
furnished by Shire specifically for use in the Registration Statement, and Shire
will reimburse Cortex (or such officer, director or controlling person, as the
case may be), for any legal or other expenses reasonably incurred in
investigating, defending, or preparing to defend any such action, proceeding or
claim.

     Promptly after receipt by any indemnified person of a notice of a claim or
the commencement of any action in respect of which indemnity is to be sought
against an indemnifying person pursuant to this Section 3.1.2, such indemnified
person shall notify the indemnifying person in writing of such claim or of the
commencement of such action, and, subject to the provisions hereinafter stated,
in case any such action shall be brought against an indemnified person and such
indemnifying person shall have been notified thereof, such indemnifying person
shall be entitled to participate therein, and, to the extent it shall wish, to
assume the defense thereof, with counsel reasonably satisfactory to such
indemnified person. After notice from the indemnifying person to such
indemnified persons of its election to assume the defense thereof, such
indemnifying person shall not be liable to such indemnified person for any legal
expenses subsequently incurred by such indemnified person in connection with the
defense thereof; provided, however, that if there exists or shall exist a
conflict of interest that would make it inappropriate, on the advice of counsel
to the indemnified person, for the same counsel to represent both the
indemnified person and such indemnifying person or any officer, director,
employee, agent, affiliate or person deemed to be in control of such
indemnifying person within the meaning of either Section 15 of the Securities
Act or Section 20 of the Exchange Act, the indemnified person shall be entitled
to retain its own counsel at the expense of such indemnifying person. It is
understood, however, that Cortex shall, in connection with any one such action,
suit or proceeding or separate but substantially similar or related actions,

                                       6
<PAGE>

suits, or proceedings in the same jurisdiction arising out of the same general
allegations or circumstances, be liable for the reasonable fees and expenses of
only one separate firm of attorneys (in addition to any local counsel) at any
time for all such indemnified parties not having actual or potential differing
interests with Cortex or among themselves.

     3.2   "Stand-Off" Agreement.  If Shire holds any Shares at such time as
           ---------------------
Cortex proposes to offer shares of its Common Stock or other securities for sale
in a registered public offering, then Shire agrees not to sell or otherwise
transfer or dispose of any such Shares or other securities of Cortex held by it
during the period commencing 10 days prior to, and expiring 90 days after, such
registered public offering has become effective. Cortex may impose stop transfer
instructions with respect to the Shares or other securities subject to the
foregoing restriction until the end of any stand-off period.

     3.3  Registration Rights Subject to Existing Rights; Termination. Shire's
          -----------------------------------------------------------
registration rights under this Article 3 shall be subject to and limited by
existing registration rights granted to certain investors in Cortex holding
piggyback registration rights. Shire's registration rights hereunder shall
terminate as to any Shares when such Shares have been sold pursuant to a
registration statement or may be sold without registration pursuant to Rules 144
or 144A, or otherwise under the Securities Act.

                       ARTICLE 4:  STANDSTILL COVENANTS.

     4.1  Standstill Agreement.  Shire agrees that, for a period of three (3)
          --------------------
years following the Closing Date (the "Standstill Period"), unless it has
obtained the prior written consent of Cortex, it will not

               (a) own or acquire, directly or indirectly, by purchase or
otherwise, of record or beneficially, any voting securities of Cortex, or rights
or options to acquire voting securities of Cortex, if after such acquisition
(and giving effect to the exercise of any such rights or options) Shire would
own of record or beneficially in the aggregate ten percent (10%) or more of the
voting securities of Cortex (assuming the exercise of all outstanding rights to
acquire voting securities held by Shire) (the "10 Percent Limit"); provided that
notwithstanding the provisions of this clause (a), if the number of shares of
outstanding voting securities is reduced or if the aggregate ownership of Shire
is increased as a result of a recapitalization of Cortex or as a result of any
other action taken by Cortex, Shire will not be required to dispose of any of
its holdings of voting securities even though such action resulted in Shire's
ownership exceeding the percentage of voting securities which the Investor would
then be permitted to own. In the event that Shire owns in the aggregate more
than the 10 Percent Limit due to a repurchase by Cortex of any of its Common
Stock, Cortex shall, at Shire's option, repurchase that number of shares of its
Common Stock from Shire necessary to reduce Shire's ownership of Cortex's Common
Stock below the 10 Percent Limit, at the current market price. Except as
otherwise provided above, if Shire shall at any time during the Standstill
Period own in the aggregate in excess of the maximum percentage of the voting
securities at the time permitted by this clause (a), Shire shall sell as
promptly as practicable under the circumstances sufficient voting securities so
that after such sale Shire shall not own in the aggregate more than the
applicable maximum permitted percentage of voting securities (provided, however,
that the foregoing paragraph shall not be deemed to limit Cortex's remedies in
the event that the excess voting securities were acquired in violation of this
Section);

                                       7
<PAGE>

          (b)  "solicit" proxies with respect to voting securities under any
circumstances or become a "participant" in any "election contest" relating to
the election of directors of Cortex, as such terms are defined in Regulation 14A
under the Exchange Act, deposit any voting securities in a voting trust or
subject them to a voting agreement or other agreement of similar effect;

          (c)  initiate, propose or otherwise solicit stockholders for the
approval of one or more stockholder proposals at any time, or induce or attempt
to induce any other person to initiate any stockholder proposal; or

          (d)  take any action individually or jointly with any partnership,
limited partnership, syndicate, or other group or assist any other person,
corporation, entity or group in taking any action it could not take individually
under the terms of this Agreement.

     4.2  Mergers, Tender Offers or Similar Transactions.  Shire agrees that,
          ----------------------------------------------
for a period of three (3) years following the Closing Date, it will not

          (a)  directly or indirectly, without the prior approval of Cortex's
Board of Directors, solicit or encourage any person to propose a business
combination or similar transaction with, or a change of control of, Cortex or to
make a tender offer for shares of Cortex's Common Stock or other voting
securities; and

          (b)  directly or indirectly, without the prior approval of Cortex's
Board of Directors, publicly (or in a manner requiring Cortex to disclose
publicly) (i) propose any business combination or similar transaction with, or a
change of control of, Cortex; (ii) make or propose a tender offer for shares of
Common Stock or other voting securities of Cortex; (iii) otherwise act to seek
control of or influence Cortex's Board of Directors or the management, policies
or affairs of Cortex; or (iv) propose any amendment to or waiver under this
Section which would permit Shire to acquire additional Common Stock or other
voting securities other than those presently permitted under this Section.

     4.3  Affiliates of Shire.  Shire represents to Cortex that there is no
          -------------------
Affiliate of Shire which, as of the date of this Agreement, owns of record or
beneficially any (a) Common Stock or other voting securities of Cortex or (b)
any other securities convertible or exchangeable (with or without the payment of
additional consideration) into voting securities of Cortex. Shire covenants to
Cortex that, if at any time while this Article 4 is in effect, any Affiliate of
Shire becomes or intends to become the beneficial owner, as defined in
regulations promulgated by the Commission, of any Common Stock or voting
securities of Cortex, or any securities convertible or exchangeable into voting
securities, Shire will, whether prior to such ownership if possible, or, if not
possible, as soon as practicable after such ownership, cause such Affiliate to
agree to be bound by Section 4 of this Agreement.

     4.4  Equitable Remedies.  Shire agrees that irreparable damage would occur
          ------------------
if any provision of this Article 4 were not performed in accordance with its
specific terms or were otherwise breached. It is accordingly agreed that Cortex
shall be entitled to an injunction or injunctions to prevent breaches of this
Article 4 and to enforce specifically the terms and provisions hereof in any
court of the United States or any state thereof having jurisdiction, in addition
to any other remedy to which it may be entitled at law or equity. Shire agrees
to waive and hereby waives any requirement for the securing or posting of any
bond in connection with the obtaining of any such injunctive or other equitable
relief.

                                       8
<PAGE>

 ARTICLE 5:  SURVIVAL OF REPRESENTATIONS, WARRANTIES AND AGREEMENTS

     5.1  Notwithstanding any investigation made by any party to this Agreement,
all covenants, agreements, representations and warranties made by Cortex and
Shire herein shall survive the execution of this Agreement, the delivery to
Shire of the Shares being purchased and the payment therefor, except to the
extent otherwise provided herein.

                           ARTICLE 6: MISCELLANEOUS



     6.1  Notices. Any consent, notice or report required or permitted to be
          -------
given or made under this Agreement by one of the parties hereto to the other
shall be in writing, delivered personally or by facsimile (and promptly
confirmed by telephone, personal delivery or courier) or courier, postage
prepaid (where applicable), addressed to such other party at its address
indicated below, or to such other address as the addressee shall have last
furnished in writing to the addressor and shall be effective upon receipt by the
addressee.

          If to Cortex:      Cortex Pharmaceuticals, Inc.
                             15241 Barranca Parkway
                             Irvine, California 92618  U.S.A.
                             Telephone:  (949) 727-3157
                             Telecopy:  (949) 727-3657

                             Attention:  Maria S. Messinger

          with a copy to:    Stradling Yocca Carlson & Rauth
                             660 Newport Center Drive, Suite 1600
                             Newport Beach, California 92660
                             Attention:  Lawrence B. Cohn
                             Telephone:  (949) 725-4132
                             Telecopy:   (949) 725-4100

          If to Shire:       Shire Pharmaceuticals Group, plc

                             East Anton, Andover
                             Hampshire, SP10 5RG ENGLAND
                             Telephone: (011) 44-1264-333455
                             Telecopy:  (011) 44-1264-333460
                             Attention: Company Secretary

     6.2  Entire Agreement.  This Agreement, together with the Option Agreement,
          ----------------
contains the entire understanding of the parties with respect to the subject
matter hereof. All express or implied agreements and understandings, either oral
or written, heretofore made are expressly merged in and made a part of this
Agreement.

     6.3  Assignment. This Agreement may not be assigned or otherwise
          ----------
transferred by either Party without the prior written consent of the other
Party, which consent shall not be unreasonably withheld or delayed; provided,
however, that each of the Parties may, without such consent, assign this
Agreement and its rights and obligations hereunder to its Affiliates or in
connection with the transfer or sale of all or substantially all of its
business, or in the event of its merger or consolidation or change in control or
similar transaction (which shall be deemed an assignment). Any purported

                                       9
<PAGE>

assignment in violation of the preceding sentences shall be void. Any permitted
assignee shall assume all obligations of its assignor under this Agreement in
writing.

     6.4  Amendments and Waivers.  Each party hereby agrees that it does not
          ----------------------
intend to violate any public policy, statutory or common laws, rules,
regulations, treaty or decision of any government agency or executive body
thereof of any country or community or association of countries. should one or
more provisions of this Agreement be or become invalid, the Parties hereto shall
substitute, by mutual consent, valid provisions for such invalid provisions
which valid provisions in their economic effect are sufficiently similar to the
invalid provisions that it can be reasonably assumed that the Parties would have
entered into this Agreement with such valid provisions. In case such valid
provisions cannot be agreed upon, the invalidity of one or several provisions of
this Agreement shall not affect the validity of this Agreement as a whole,
unless the invalid provisions are of such essential importance to this Agreement
that it is to be reasonably assumed that the Parties would not have entered into
this Agreement without the invalid provisions.

     6.5  Headings.  The headings of the various sections of this Agreement have
          --------
been inserted for convenience of reference only and shall not be deemed to be
part of this Agreement.

     6.6  Severability.  In case any provision contained in this Agreement
          ------------
should be invalid, illegal or unenforceable in any respect, the validity,
legality and enforceability of the remaining provisions contained herein shall
not in any way be affected or impaired thereby.

     6.7  Governing Law, Venue.  This Agreement shall be governed by, and
          --------------------
construed in accordance with, the laws of the State of California and the United
States, as though made and to be fully performed therein without regard to
conflicts of laws principles thereof. All disputes with respect to this
Agreement and the subject matter hereof shall be heard exclusively in the state
or federal courts in Orange County, California, and the parties agree to the
jurisdiction of such courts.

     6.8  Counterparts.  This Agreement may be executed in two or more
          ------------
counterparts, each of which shall be deemed an original, but all of which
together shall constitute one and the same instrument.

     6.9  Expenses.  Except as otherwise specifically provided herein, each
          --------
party shall bear its own expenses in connection with this Agreement.

     6.10 Publicity.  Neither party hereto shall issue any press releases or
          ---------
otherwise make any public statement with respect to the transactions
contemplated by this Agreement without the prior written consent of the other
party, except as may be required by applicable law or regulation.

     6.11 Confidentiality.  Shire acknowledges and agrees that any information
          ---------------
or data it has acquired from Cortex, not otherwise properly in the public
domain, was received in confidence. Shire agrees not to divulge, communicate or
disclose, except as may be required by law or for the performance of this
Agreement, or use to the detriment of Cortex or for the benefit of any other
person or persons, or misuse in any way, any confidential information of Cortex.

                                      10
<PAGE>

     IN WITNESS WHEREOF, the parties hereto have caused this Agreement to be
executed by their duly authorized representatives as of the day and year first
above written.



                                                CORTEX PHARMACEUTICALS, INC.


                                                By:   ________________________

                                                Name: ________________________

                                                Its:  ________________________


                                                SHIRE PHARMACEUTICALS GROUP, plc


                                                By:   ________________________

                                                Name: ________________________

                                                Its:  ________________________

                                      11
<PAGE>

                                   EXHIBIT C

Under embargo until 1pm (UK), 8am (US ET)
19 April 2000


                Cortex and Shire Announce Agreement to Evaluate
                      Ampakine CX516 for the Treatment of
                Attention Deficit Hyperactivity Disorder (ADHD)


Andover, UK- 19 April 2000 - Shire Pharmaceuticals Group plc (LSE : SHP.L,
NASDAQ : SHPGY) and Cortex Pharmaceuticals, Inc. (OTC.BB: CORX) announced today
that they have signed an option agreement under which Shire will evaluate the
use of Cortex's Ampakine CX516 for the treatment of Attention Deficit
Hyperactivity Disorder (ADHD).  Under the terms of the agreement, Shire will
undertake a double-blind, placebo-controlled evaluation of CX516 in ADHD
patients. In exchange for the option, Cortex will receive US $870,000 and will
issue common stock to Shire. In addition, Shire will pay $130,000 and purchase
study drug from Cortex. Shire will be responsible for all costs associated with
the clinical trial.

If the study proves effective, Shire has the right to convert its option into an
exclusive worldwide license for the Ampakines/(R)/ for ADHD under a development
and licensing agreement. Should Shire elect to execute this agreement, Shire
will bear all future developmental costs. Cortex would receive an upfront fee,
milestone payments based on successful clinical and commercial development,
research support for additional Ampakines and royalties on sales.

"Shire is one of the leading companies in the field of ADHD and we believe that
they are an excellent and aggressive partner for developing this potential
Ampakine application," stated Vincent F. Simmon, Ph.D., President and Chief
Executive Officer of Cortex.  "Ampakines have not been previously tested in
patients with ADHD, but notable improvements were observed in clinical and
neuropsychiatric measures of attention, distractibility, memory and cognition in
a recently completed double-blind study of Ampakine CX516 in patients with
schizophrenia.  Patients with ADHD typically have impairments in each of these
critical areas.  The Ampakines could represent a novel, non-controlled (not
regulated by the Drug Enforcement Agency) approach for treating ADHD."

Shire currently markets Adderall and Dextrostat for ADHD, which together have
more than a 30% share of the US market, according to US IMS.   Dr. Wilson
Totten, Group R&D Director of Shire stated, "The Ampakines may represent a
completely new pharmacological approach to this disease and may have the
potential to improve the management of patients with ADHD and related
disorders." Rolf Stahel, Chief Executive of Shire commented, "We see the
Ampakines as a significant potential strengthening of our global ADHD strategy."
<PAGE>

                                   -   END -
For further information please contact:

Shire Pharmaceuticals Group, plc:

     Dr Michael Gaitonde                     David Yates / Sophie Pender-Cudlip
     Investor Relations                      Financial Dynamics
     Shire Pharmaceuticals Group, plc        Shire Pharmaceuticals Group, plc
     + 44 1264 348552                        + 44 171 831 3113

Cortex Pharmaceuticals, Inc.:

     Vincent F. Simmon, Ph.D.                Bruce Russell
     President and CEO                       Investor Relations
     Cortex Pharmaceuticals, Inc.            Russell Communications Group
     001 (949) 727-3157                      001 (310) 216-1414

Notes to editors

Shire Pharmaceuticals Group plc

Shire is an international specialty pharmaceutical company with a strategic
focus on four therapeutic areas: central nervous system disorders, metabolic
diseases, oncology and gastroenterology.  The group has sales and marketing
infrastructure with a broad portfolio of products targeting the US, Canada, UK,
Republic of Ireland, France, Germany and Italy, with plans to add other key
markets in due course.  Shire's global research and development expertise has
already provided three marketed products, whilst the current pipeline of 14
projects includes one project in registration and a significant number post
Phase II. Shire is actively searching to acquire further marketed products and
development projects to enhance the potential for future growth, both
organically and by acquisition.  Website:  http://www.shire.com/
                                           ---------------------

Cortex Pharmaceuticals, Inc.

Cortex, located in Irvine, California, is a development stage neuroscience
company pioneering a new class of proprietary pharmaceuticals called Ampakines,
which act to increase the strength of signals at connections between brain
cells. Disruption of these connections is believed to be associated with a
number of psychiatric and neurodegenerative diseases and disorders including
schizophrenia, depression and Alzheimer's disease. The agreement with Shire
marks the third mental health disorder under development using Cortex's Ampakine
technology. In January 1999, the Company licensed the rights to its Ampakine
technology to NV Organon, a division of Akzo Nobel, for use in schizophrenia and
depression. A recently completed double-blind, placebo-controlled study
conducted by Don Goff, M.D. at Harvard's Massachusetts General Hospital in
patients with schizophrenia indicated improvement in a number of
<PAGE>

symptoms also common to patients with ADHD. Cortex is currently in advanced
discussions regarding another licensing opportunity for the use of Ampakines in
neurodegenerative disorders including mild cognitive impairment and Alzheimer's
disease. Website: http://www.cortexpharm.com/
                  ---------------------------


Attention Deficit Hyperactivity Disorder (ADHD)

Attention deficit hyperactivity disorder (ADHD) is a central nervous system
disorder of unknown cause and is characterized by varying degrees of
inattention, impulsiveness and hyperactivity.  ADHD is primarily a childhood
disorder, although it is increasingly being recognized as continuing through
adolescence and into adulthood.  It is estimated that between three and five
percent of children in the US suffer from the condition.  US Drug Enforcement
Agency Schedule II products, specifically methylphenidate and amphetamines, are
currently the only approved first line treatments for ADHD available.  For a
full discussion of ADHD treatment options, please see the NIH Consensus document
referenced below.


Source:    Diagnosis and Treatment of Attention Deficit Hyperactivity Disorder
           National Institutes of Health -- Consensus Development Statement,
           November 16-18, 1998

           http://odp.od.nih.gov/consensus/cons/110/110 statement.htm
           ----------------------------------------------------------

THE "SAFE HARBOR STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT
OF 1995. The statements in this press release that are not historical facts are
forward-looking statements that involve risks and uncertainties, including but
not limited to, risks associated with the inherent uncertainty of pharmaceutical
research, product development and commercialization, the impact of competitive
products, patents, and other risks and uncertainties, including those detailed
from time to time in periodic reports, including the F-4 Prospectus and the
Annual Report filed on Form 10K by Shire with the Securities and Exchange
Commission.
<PAGE>

                         CONFIDENTIAL PORTIONS OMITTED
                         -----------------------------




                                   EXHIBIT D
                                   ---------

                           STOCK PURCHASE AGREEMENT

                                    between

                         CORTEX PHARMACEUTICALS, INC.

                                      and

                       SHIRE PHARMACEUTICALS GROUP, plc

                        dated as of ____________, 2000



                              (License Agreement)
<PAGE>

                           STOCK PURCHASE AGREEMENT

     THIS STOCK PURCHASE AGREEMENT (the "Agreement") dated as of ____________,
2000 (the "Effective Date") is made between CORTEX PHARMACEUTICALS, INC., having
its principal offices at 15241 Barranca Parkway, Irvine, California ("Cortex")
U.S.A., and Shire Pharmaceuticals Group, plc., having its principal offices at
East Anton, Andover, Hampshire, SP10 5RG England ("Shire").  All terms not
otherwise defined herein are defined in either the Option Agreement or the
Development and License Agreement described below.  The execution and delivery
of this Agreement shall constitute the "Closing".

                                R E C I T A L S

     A.  Cortex possesses know-how, expertise and rights to issued United States
patents and patent applications with corresponding foreign filed patent
applications pertaining to a class of proprietary pharmaceuticals called
Ampakines(R).

     B.  Cortex and Shire have on even date herewith entered into a Development
and License Agreement (the "Development and License Agreement").  In connection
with the Development and License Agreement, Shire shall purchase Common Stock of
Cortex on the terms and conditions set forth herein.

     NOW THEREFORE, in consideration of the premises and of the covenants herein
contained, the parties hereto mutually agree as follows:

                           1  SALE OF CORTEX SHARES

1.1  Sale of Common Stock. Subject to the satisfaction of the terms and
     --------------------
     conditions of the Closing set forth herein and in reliance upon the
     respective representations and warranties of the parties set forth herein
     or in any document delivered pursuant hereto, Cortex agrees to sell to
     Shire upon the Closing [*]. The shares of Common Stock which are to be
     purchased pursuant to this Article referred to herein as the "Shares".

1.2  Delivery of the Shares at the Closing.  The Closing for the purchase of the
     -------------------------------------
shares shall occur at a place and time (the "Closing Date") to be agreed upon by
Cortex and Shire. At the Closing, Shire shall pay to Cortex the aggregate
purchase price for the Shares being purchased hereunder and Cortex shall deliver
to Shire one or more stock certificates registered in the name of Shire, or in
such nominee name(s) as designated in writing by Shire, representing the number
of Shares being purchased. Cortex's obligation to complete the purchase and sale
of the Shares and deliver such stock certificate(s) to Shire at the Closing
shall be subject to the following conditions, any one or more of which may be
waived by Cortex: (a) receipt by Cortex of a certified or bank check or wire
transfer in the full amount of the purchase price for the Shares being purchased
hereunder and (b) the accuracy in all material respects of the representations
and warranties made by Shire herein and the fulfillment in all material respects
of those undertakings of Shire to be fulfilled prior to the Closing. Shire's
obligation to accept delivery of such stock certificate(s) and to pay for the
Shares evidenced thereby shall be subject to the accuracy in all material
respects of the


*CONFIDENTIAL PROVISIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION

                                       1
<PAGE>

representations and warranties made by Cortex herein and the fulfillment in all
material respects of those undertakings of Cortex to be fulfilled prior to the
Closing, any one or more of which conditions may be waived by Shire.

                    2       REPRESENTATIONS AND WARRANTIES

2.1  Representations, Warranties and Covenants of Cortex.  Cortex hereby
     ---------------------------------------------------
     represents and warrants to, and covenants with, Shire as follows:

2.1.1  Organization and Qualification.  Cortex is a corporation duly organized,
       ------------------------------
       validly existing and in good standing under the laws of the State of
       Delaware and has all requisite corporate power and authority to conduct
       its business as currently conducted.

2.1.2  Due Execution, Delivery and Performance of the Agreement.  Cortex's
       --------------------------------------------------------
       execution, delivery and performance of this Agreement (a) has been duly
       authorized under Delaware law by all requisite corporate action by
       Cortex, and (b) will not violate any law or the Certificate of
       Incorporation or Bylaws of Cortex or any subsidiary or any provision of
       any material indenture, mortgage, agreement, contract or other material
       instrument to which Cortex or any subsidiary is a party or by which
       Cortex or any of their respective properties or assets is bound as of the
       date hereof, or result in a breach of or constitute (upon notice or lapse
       of time or both) a default under any such indenture, mortgage, agreement,
       contract or other material instrument or result in the creation or
       imposition of any lien, security interest, mortgage, pledge, charge or
       other encumbrance, of any material nature whatsoever, upon any properties
       or assets of Cortex or any subsidiary. Upon its execution and delivery,
       and assuming the valid execution thereof by Shire, the Agreement will
       constitute a valid and binding obligation of Cortex, enforceable against
       Cortex in accordance with its terms, except as enforceability may be
       limited by applicable bankruptcy, insolvency, reorganization, moratorium
       or similar laws affecting creditors' and contracting parties' rights
       generally and except as enforceability may be subject to general
       principles of equity (regardless of whether such enforceability is
       considered in a proceeding in equity or at law).

2.1.3  Issuance, Sale and Delivery of the Shares.  The shares have been duly
       -----------------------------------------
       authorized and reserved for issuance to Shire by all necessary corporate
       action. When issued and paid for, the Shares to be sold hereunder by
       Cortex will be validly issued and outstanding, fully paid and non-
       assessable.

2.1.4  Additional Information.  Cortex represents and warrants that all reports
       ----------------------
       filed by Cortex with the Securities and Exchange Commission (the
       "Commission") since January 1, [INSERT YEAR END TWO YEARS PRIOR TO
       EFFECTIVE DATE] pursuant to the reporting requirements of the Securities
       Exchange Act of 1934, as amended (the "Exchange Act"), when filed, did
       not contain any untrue statement of a material fact or omit to state any
       material fact required to be stated therein or necessary to make the
       statements therein, in light of the circumstances in which they were
       made, not misleading.

2.1.5  No Material Changes.  As of the date hereof, there has been no material
       -------------------
       adverse change in the financial condition or results of operations of
       Cortex since the filing date of Cortex's last report with the Commission
       pursuant to the reporting requirements of the Exchange Act.

2.2  Representations, Warranties and Covenants of Shire.
     --------------------------------------------------

                                       2
<PAGE>

2.2.1  Investment Considerations.  Shire represents and warrants to, and
       -------------------------
       covenants with, Cortex that:

          2.2.1.1   Shire has the business experience to protect its interests
in connection with this investment and has requested, received, reviewed and
considered all information it deems relevant in making an informed decision to
purchase the Shares;

          2.2.1.2   Shire is acquiring the Shares for its own account for
investment only and with no present intention of distributing any of such Shares
within the meaning of Section 2(11) of the Securities Act of 1933 (the
"Securities Act") or any arrangement or understanding with any other persons
regarding the distribution of such Shares (within the meaning of the Securities
Act);

          2.2.1.3   Shire understands that the Shares it is purchasing are
"restricted securities" under the federal securities laws inasmuch as they are
being acquired from Cortex in a transaction not involving a public offering and
that under such laws and applicable regulations such securities may be resold
without registration under the Securities Act only in certain limited
circumstances;

          2.2.1.4   Shire will not, directly or indirectly, offer, sell, pledge,
transfer or otherwise dispose of (or solicit any offers to buy, purchase or
otherwise acquire or take a pledge of) any of the Shares except in compliance
with the Securities Act and the rules and regulations promulgated thereunder.
Without in any way limiting the representations set forth above, Shire further
agrees not to make any disposition of all or any portion of the Shares for a
period of the longer of (i) two (2) years following the date of acquisition of
the Shares, or (ii) the end of the Research Phase as defined in the Development
and License Agreement, and, after such time, only if (x) there is then in effect
a Registration Statement under the Securities Act covering such proposed
disposition and such disposition is made in accordance with such Registration
Statement; or (y) (A) Shire shall have notified Cortex of the proposed
disposition and shall have furnished Cortex with a detailed statement of the
circumstances surrounding the proposed disposition, and (B) if requested by
Cortex, Shire shall have furnished Cortex with an opinion of counsel, reasonably
satisfactory to Cortex and its counsel, that such disposition will not require
registration of such shares under the Securities Act, provided that Cortex shall
not require such opinion to the extent such disposition is in accordance with
Rule 144.  In addition, Shire will not dispose of more than One Hundred Thousand
(100,000) Shares in any calendar month, including for such calculation, any
shares of Common Stock Shire acquired pursuant to the Stock Purchase Agreement
April 19, 2000, (the "Prior Stock Purchase Agreement"), irrespective of its
disposition of shares in any prior calendar month.

          2.2.1.5   Shire qualifies as an "accredited investor" within the
meaning of Rule 501 of Regulation D promulgated under the Securities Act; and

          2.2.1.6   It is understood that the certificates evidencing the Shares
shall bear the following legend:

          "These securities have not been registered under the
          Securities Act of 1933. They may not be sold, offered for
          sale, pledged or hypothecated in the absence of a
          registration statement in effect with respect to the
          securities under such Act or, if requested by Cortex, an
          opinion of counsel reasonably satisfactory to Cortex and its
          counsel, that such registration is not required under such
          Act."

                                  3
<PAGE>

       2.2.2   Due Execution, Delivery and Performance of the Agreement. Shire
               --------------------------------------------------------
further represents and warrants to, and covenants with, Cortex that (a) Shire is
a public limited company duly organized, validly existing and in good standing
under the laws of England and Wales and has full right, power, authority and
capacity to enter into this Agreement and to consummate the transactions
contemplated hereby and has taken all necessary action to authorize the
execution, delivery and performance of this Agreement, (b) the execution,
delivery and performance of this Agreement will not violate any law or the
Articles of Association of Shire or any subsidiary or any provision of any
material indenture, mortgage, agreement, contract or other material instrument
to which Shire or any subsidiary is a party or by which Shire, any subsidiary,
or any of their respective properties or assets is bound as of the date hereof,
or result in a breach of or constitute (upon notice or lapse of time or both) a
default under any such indenture, mortgage, agreement, contract or other
material instrument or result in the creation or imposition of any lien,
security interest, mortgage, pledge, charge or encumbrance, of any material
nature whatsoever, upon any assets of Shire or any subsidiary and (c) upon the
execution and delivery of this Agreement, this Agreement shall constitute a
valid and binding obligation of Shire enforceable in accordance with its terms,
except as enforceability may be limited by applicable bankruptcy, insolvency,
reorganization, moratorium or similar laws affecting creditors' and contracting
parties' rights generally and except as enforceability may be subject to general
principles of equity (regardless of whether such enforceability is considered in
a proceeding in equity or at law).

                          3   REGISTRATION RIGHTS

3.1  Registration Rights.  Cortex covenants and agrees as follows:
     -------------------

       3.1.1   Requested Registrations. At any time after the end of the
               -----------------------
Research Phase as defined in the Development and License Agreement, and subject
to the conditions herein set forth, Shire shall have the right to require Cortex
to effect the registration of Shares on a registration statement under the
Securities Act by giving Cortex written notice requesting such registration and
specifying the number of Shares proposed to be sold and the proposed plan for
distribution of such Shares; provided, however, that such request shall cover at
least [*] Shares (including any shares acquired by Shire under the Prior Stock
Purchase Agreement). Shire shall be entitled to one requested registration on an
appropriate registration form for a registered offer (including in such
limitation, any registration requested under the Prior Stock Purchase
Agreement). If and whenever Cortex shall be required by the provisions of this
Section 3.1.1 to effect the registration of any Shares hereunder, Cortex will,
as expeditiously as possible:

       3.1.1.1 use its best efforts to prepare and file a registration
statement, giving effect to the plan of distribution of the Shares proposed to
be sold, and use its best efforts to cause such registration statement to become
effective in order that Shire may sell its Shares in accordance with the
proposed plan of distribution;

* CONFIDENTIAL PROVISIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION

                                       4
<PAGE>

       3.1.1.2  prepare and file with the Commission such amendments and
supplements to such registration statement and the prospectus used in connection
therewith as may be necessary to keep such registration statement effective and
advise Shire promptly of any proposal to amend or supplement the registration
statement and to comply with the provisions of the Securities Act with respect
to the offer of the Shares covered by such registration statement during the
period required for distribution of the Shares, which period shall not be in
excess of nine (9) months from the effective date of such registration
statement;

       3.1.1.3  furnish Shire such number of copies of such prospectus as it may
reasonably request in order to facilitate the sale of the Shares;

       3.1.1.4  file documents required of Cortex for blue sky clearance in
states specified in writing by Shire; provided, however, that Cortex shall not
be required to qualify to do business or consent to service of process in any
jurisdiction in which it is now not so qualified or has not so consented; and

       3.1.1.5  use it best efforts to prevent the issuance of any stop order
with respect to any registration statement and, if any stop order is issued, to
obtain the lifting thereof at the earliest possible moment;

       3.1.1.6  file all documents required to be filed with the Commission
pursuant to the Exchange Act;

       3.1.1.7  have the Shares listed on the NASDAQ OTC Bulletin Board, or such
other exchange as the Common Stock may then be listed on;

       3.1.1.8  bear all expenses in connection with the procedures set forth in
paragraphs (a) through (d) of this Section 6.1 and the registration of the
Shares pursuant to the registration statement, other than fees and expenses, if
any, of counsel or other advisors to Shire.

       If at the time of any request to register Shares pursuant to this Section
6.1 Cortex is engaged or has fixed plans to engage within 60 days of the date of
receipt of the request in a registered public offering, or is engaged in any
other activity which, in the good faith determination of Cortex's Board of
Directors, would be adversely affected by the demand registration, then Cortex
may at its option direct that such request be delayed for a period not in excess
of 90 days from the closing of such offering or the date of Cortex's Board of
Directors' determination, as the case may be.

3.1.2  Indemnification.  For the purpose of this Section 3.1.2,
       ---------------

       3.1.2.1  the term "Selling Stockholder" shall mean Shire and any officer,
director, employee, agent, affiliate or person deemed to be in control of such
person within the meaning of Section 15 of the Securities Act or Section 20 of
the Exchange Act;

       3.1.2.2  the term "Registration Statement" shall mean any final
prospectus, exhibit, supplement or amendment included in or relating to the
registration statement referred to in Section 6.1; and

       3.1.2.3  the term "untrue statement" shall mean any untrue statement or
alleged untrue statement of, or any omission or alleged omission to state, in
the Registration Statement a material fact required to be stated therein or
necessary to make the statements therein, in the light of the circumstances
under which they were made, not misleading.

                                       5
<PAGE>

     Cortex agrees to indemnify and hold harmless each Selling Stockholder from
and against any losses, claims, damages or liabilities to which such Selling
Stockholder may become subject (under the Securities Act or otherwise) insofar
as such losses, claims, damages or liabilities (or actions or proceedings in
respect thereof) arise out of, or are based upon, any untrue statement of a
material fact contained in the Registration Statement on or after the effective
date thereof, or arise out of any failure by Cortex to fulfill any undertaking
included in the Registration Statement and Cortex will reimburse such Selling
Stockholder for any reasonable legal or other expenses reasonably incurred in
investigating, defending or preparing to defend any such action, proceeding or
claim; provided, however, that Cortex shall not be liable in any such case to
the extent that such loss, claim, damage or liability arises out of, or is based
upon, an untrue statement made in such Registration Statement in reliance upon
and in conformity with written information furnished to Cortex by or on behalf
of such Selling Stockholder specifically for use in the Registration Statement,
or any statement or omission in any Prospectus that is corrected in any
subsequent Prospectus that was delivered to Shire prior to the pertinent sale or
sales by Shire.

     Shire agrees to indemnify and hold harmless Cortex (and each person, if
any, who controls Cortex within the meaning of Section 15 of the Securities Act,
each officer of Cortex who signs the Registration Statement and each director of
Cortex) from and against any losses, claims, damages or liabilities to which
Cortex (or any such officer, director or controlling person) may become subject
(under the Securities Act or otherwise), insofar as such losses, claims, damages
or liabilities (or actions or proceedings in respect thereof) arise out of, or
are based upon, any untrue statement of a material fact contained in the
Registration Statement on or after the effective date thereof if such untrue
statement was made in reliance upon and in conformity with written information
furnished by Shire specifically for use in the Registration Statement, and Shire
will reimburse Cortex (or such officer, director or controlling person, as the
case may be), for any legal or other expenses reasonably incurred in
investigating, defending, or preparing to defend any such action, proceeding or
claim.

     Promptly after receipt by any indemnified person of a notice of a claim or
the commencement of any action in respect of which indemnity is to be sought
against an indemnifying person pursuant to this Section 3.1.2, such indemnified
person shall notify the indemnifying person in writing of such claim or of the
commencement of such action, and, subject to the provisions hereinafter stated,
in case any such action shall be brought against an indemnified person and such
indemnifying person shall have been notified thereof, such indemnifying person
shall be entitled to participate therein, and, to the extent it shall wish, to
assume the defense thereof, with counsel reasonably satisfactory to such
indemnified person.  After notice from the indemnifying person to such
indemnified persons of its election to assume the defense thereof, such
indemnifying person shall not be liable to such indemnified person for any legal
expenses subsequently incurred by such indemnified person in connection with the
defense thereof; provided, however, that if there exists or shall exist a
conflict of interest that would make it inappropriate, on the advice of counsel
to the indemnified person, for the same counsel to represent both the
indemnified person and such indemnifying person or any officer, director,
employee, agent, affiliate or person deemed to be in control of such
indemnifying person within the meaning of either Section 15 of the Securities
Act or Section 20 of the Exchange Act, the indemnified person shall be entitled
to retain its own counsel at the expense of such indemnifying person.  It is
understood, however, that Cortex shall, in connection with any one such action,
suit or proceeding or separate but substantially similar or related actions,
suits, or proceedings in the same jurisdiction arising out of the same general
allegations or circumstances, be liable for the reasonable fees and expenses of
only one separate firm of attorneys (in addition to any local counsel) at any
time for all such indemnified parties not having actual or potential differing
interests with Cortex or among themselves.

                                       6
<PAGE>

     3.2      "Stand-Off" Agreement. If Shire holds any Shares at such time as
              ---------------------
Cortex proposes to offer shares of its Common Stock or other securities for sale
in a registered public offering, then Shire agrees not to sell or otherwise
transfer or dispose of any such Shares or other securities of Cortex held by it
during the period commencing 10 days prior to, and expiring 90 days after, such
registered public offering has become effective. Cortex may impose stop transfer
instructions with respect to the Shares or other securities subject to the
foregoing restriction until the end of any stand-off period.

     3.3      Registration Rights Subject to Existing Rights; Termination.
              -----------------------------------------------------------
Shire's registration rights under this Article 3 shall be subject to and limited
by existing registration rights granted to certain investors in Cortex holding
piggyback registration rights. Shire's registration rights hereunder shall
terminate as to any Shares when such Shares have been sold pursuant to a
registration statement or may be sold without registration pursuant to Rules 144
or 144A, or otherwise under the Securities Act.

                           4  STANDSTILL COVENANTS.

     4.1      Standstill Agreement. Shire agrees that, for a period of three (3)
              --------------------
years following the Closing Date (the "Standstill Period"), unless it has
obtained the prior written consent of Cortex, it will not

     4.1.1.1  own or acquire, directly or indirectly, by purchase or otherwise,
of record or beneficially, any voting securities of Cortex, or rights or options
to acquire voting securities of Cortex, if after such acquisition (and giving
effect to the exercise of any such rights or options) Shire would own of record
or beneficially in the aggregate ten percent (10%) or more of the voting
securities of Cortex (assuming the exercise of all outstanding rights to acquire
voting securities held by Shire) (the "10 Percent Limit"); provided that
notwithstanding the provisions of this clause (a), if the number of shares of
outstanding voting securities is reduced or if the aggregate ownership of Shire
is increased as a result of a recapitalization of Cortex or as a result of any
other action taken by Cortex, Shire will not be required to dispose of any of
its holdings of voting securities even though such action resulted in Shire's
ownership exceeding the percentage of voting securities which the Investor would
then be permitted to own. In the event that Shire owns in the aggregate more
than the 10 Percent Limit due to a repurchase by Cortex of any of its Common
Stock, Cortex shall, at Shire's option, repurchase that number of shares of its
Common Stock from Shire necessary to reduce Shire's ownership of Cortex's Common
Stock below the 10 Percent Limit, at the current market price. Except as
otherwise provided above, if Shire shall at any time during the Standstill
Period own in the aggregate in excess of the maximum percentage of the voting
securities at the time permitted by this clause (a), Shire shall sell as
promptly as practicable under the circumstances sufficient voting securities so
that after such sale Shire shall not own in the aggregate more than the
applicable maximum permitted percentage of voting securities (provided, however,
that the foregoing paragraph shall not be deemed to limit Cortex's remedies in
the event that the excess voting securities were acquired in violation of this
Section);

     4.1.1.2  "solicit" proxies with respect to voting securities under any
circumstances or become a "participant" in any "election contest" relating to
the election of directors of Cortex, as such terms are defined in Regulation 14A
under the Exchange Act, deposit any voting securities in a voting trust or
subject them to a voting agreement or other agreement of similar effect;

                                       7
<PAGE>

     4.1.1.3  initiate, propose or otherwise solicit stockholders for the
approval of one or more stockholder proposals at any time, or induce or attempt
to induce any other person to initiate any stockholder proposal; or

     4.1.1.4  take any action individually or jointly with any partnership,
limited partnership, syndicate, or other group or assist any other person,
corporation, entity or group in taking any action it could not take individually
under the terms of this Agreement.

4.2  Mergers, Tender Offers or Similar Transactions.  Shire agrees that, for a
     ----------------------------------------------
period of three (3) years following the Closing Date, it will not

     4.2.1.1  directly or indirectly, without the prior approval of Cortex's
Board of Directors, solicit or encourage any person to propose a business
combination or similar transaction with, or a change of control of, Cortex or to
make a tender offer for shares of Cortex's Common Stock or other voting
securities; and

     4.2.1.2  directly or indirectly, without the prior approval of Cortex's
Board of Directors, publicly (or in a manner requiring Cortex to disclose
publicly) (i) propose any business combination or similar transaction with, or a
change of control of, Cortex; (ii) make or propose a tender offer for shares of
Common Stock or other voting securities of Cortex; (iii) otherwise act to seek
control of or influence Cortex's Board of Directors or the management, policies
or affairs of Cortex; or (iv) propose any amendment to or waiver under this
Section which would permit Shire to acquire additional Common Stock or other
voting securities other than those presently permitted under this Section.

     4.3      Affiliates of Shire.  Shire represents to Cortex that there is no
              -------------------
Affiliate of Shire which, as of the date of this Agreement, owns of record or
beneficially any (a) Common Stock or other voting securities of Cortex or (b)
any other securities convertible or exchangeable (with or without the payment of
additional consideration) into voting securities of Cortex.  Shire covenants to
Cortex that, if at any time while this Article 4 is in effect, any Affiliate of
Shire becomes or intends to become the beneficial owner, as defined in
regulations promulgated by the Commission, of any Common Stock or voting
securities of Cortex, or any securities convertible or exchangeable into voting
securities, Shire will, whether prior to such ownership if possible, or, if not
possible, as soon as practicable after such ownership, cause such Affiliate to
agree to be bound by Section 4 of this Agreement.

     4.4      Equitable Remedies.  Shire agrees that irreparable damage would
              ------------------
occur if any provision of this Article 4 were not performed in accordance with
its specific terms or were otherwise breached. It is accordingly agreed that
Cortex shall be entitled to an injunction or injunctions to prevent breaches of
this Article 4 and to enforce specifically the terms and provisions hereof in
any court of the United States or any state thereof having jurisdiction, in
addition to any other remedy to which it may be entitled at law or equity. Shire
agrees to waive and hereby waives any requirement for the securing or posting of
any bond in connection with the obtaining of any such injunctive or other
equitable relief.

           5  SURVIVAL OF REPRESENTATIONS, WARRANTIES AND AGREEMENTS

     5.1      Notwithstanding any investigation made by any party to this
Agreement, all covenants, agreements, representations and warranties made by
Cortex and Shire herein shall survive

                                       8
<PAGE>

the execution of this Agreement, the delivery to Shire of the Shares being
purchased and the payment therefor, except to the extent otherwise provided
herein.

                               6  MISCELLANEOUS

     6.1  Notices.  Any consent, notice or report required or permitted to be
given or made under this Agreement by one of the parties hereto to the other
shall be in writing, delivered personally or by facsimile (and promptly
confirmed by telephone, personal delivery or courier) or courier, postage
prepaid (where applicable), addressed to such other party at its address
indicated below, or to such other address as the addressee shall have last
furnished in writing to the addressor and shall be effective upon receipt by the
addressee.

     If to Cortex:       Cortex Pharmaceuticals, Inc.
                         15241 Barranca Parkway
                         Irvine, California 92618 U.S.A.
                         Telephone:(949) 727-3157
                         Telecopy: (949) 727-3657

     with a copy to:     Stradling Yocca Carlson & Rauth
                         660 Newport Center Drive, Suite 1600
                         Newport Beach, California 92660
                         Attention: Lawrence B. Cohn
                         Telephone:(949) 725-4132
                         Telecopy: (949) 725-4100

     If to Shire:        Shire Pharmaceuticals Group, plc
                         East Anton, Andover
                         Hampshire, SP10 5RG ENGLAND
                         Telephone:(011) 44-1264-333455
                         Telecopy: (011) 44-1264-333460
                         Attention: Nicola Proudlock

     6.2  Entire Agreement.  This Agreement, together with the Option Agreement,
          ----------------
contains the entire understanding of the parties with respect to the subject
matter hereof.  All express or implied agreements and understandings, either
oral or written, heretofore made are expressly merged in and made a part of this
Agreement.

     6.3  Assignment. This Agreement may not be assigned or otherwise
          ----------
transferred by either Party without the prior written consent of the other
Party, which consent shall not be unreasonably withheld or delayed; provided,
however, that each of the Parties may, without such consent, assign this
Agreement and its rights and obligations hereunder to its Affiliates or in
connection with the transfer or sale of all or substantially all of its
business, or in the event of its merger or consolidation or change in control or
similar transaction (which shall be deemed an assignment). Any purported
assignment in violation of the preceding sentences shall be void. Any permitted
assignee shall assume all obligations of its assignor under this Agreement in
writing.

     6.4  Amendments and Waivers. Each party hereby agrees that it does not
          ----------------------
intend to violate any policy, statutory or common laws, rules, regulations,
treaty or decision of any government agency or executive body thereof of any
country or community or association of countries. Should one or more provisions
of this Agreement be or become invalid, the Parties hereto shall substitute by

                                       9
<PAGE>

mutual consent, valid provisions for such invalid provisions which valid
provisions in their economic effect are sufficiently similar to the invalid
provisions  that it can be reasonably assumed that the Parties would have
entered into this Agreement with such valid provisions.  In case such valid
provisions cannot be agreed upon, the invalidity of one or several provisions of
this Agreement shall not affect the validity of this Agreement as a whole,
unless the invalid provisions are of such essential importance to this Agreement
that it is to be reasonably assumed that the Parties would not have entered into
this Agreement without the invalid provisions.

     6.5   Headings.  The headings of the various sections of this Agreement
           --------
have been inserted for convenience of reference only and shall not be deemed to
be part of this Agreement.

     6.6   Severability.  In case any provision contained in this Agreement
           ------------
should be invalid, illegal or unenforceable in any respect, the validity,
legality and enforceability of the remaining provisions contained herein shall
not in any way be affected or impaired thereby.

     6.7   Governing Law, Venue.  This Agreement shall be governed by, and
           --------------------
construed in accordance with, the laws of the State of California and the United
States, as though made and to be fully performed therein without regard to
conflicts of laws principles thereof. All disputes with respect to this
Agreement and the subject matter hereof shall be heard exclusively in the state
or federal courts in Orange County, California, and the parties agree to the
jurisdiction of such courts.

     6.8   Counterparts.  This Agreement may be executed in two or more
           ------------
counterparts, each of which shall be deemed an original, but all of which
together shall constitute one and the same instrument.

     6.9   Expenses.  Except as otherwise specifically provided herein, each
           --------
party shall bear its own expenses in connection with this Agreement.

     6.10  Publicity.  Neither party hereto shall issue any press releases or
           ---------
otherwise make any public statement with respect to the transactions
contemplated by this Agreement without the prior written consent of the other
party, except as may be required by applicable law or regulation.

     6.11  Confidentiality.  Shire acknowledges and agrees that any information
           ---------------
or data it has acquired from Cortex, not otherwise properly in the public
domain, was received in confidence. Shire agrees not to divulge, communicate or
disclose, except as may be required by law or for the performance of this
Agreement, or use to the detriment of Cortex or for the benefit of any other
person or persons, or misuse in any way, any confidential information of Cortex.

                                      10
<PAGE>

IN WITNESS WHEREOF, the parties hereto have caused this Agreement to be executed
by their duly authorized representatives as of the day and year first above
written.

                                           CORTEX PHARMACEUTICALS, INC.

                                           By:   _______________________________
                                           Name: _______________________________
                                           Its:  _______________________________



                                           SHIRE PHARMACEUTICALS GROUP, plc



                                           By:   _______________________________
                                           Name: _______________________________
                                           Its:  _______________________________

                                      11
<PAGE>

                                   EXHIBIT E



                                PATENT COUNTRIES
<PAGE>

                                   EXHIBIT F



                              THIRD PARTY LICENSES