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                                                                   Exhibit 10.28





                                December 1, 1999

Cambridge NeuroScience, Inc.
One Kendall Square, Building 700
Cambridge, MA 02139

         Re:      Collaborative Research, Development and Marketing Agreement
                  dated as November 20, 1996 (the "Agreement")
                  -----------------------------------------------------------

Ladies and Gentlemen:

         This letter is to document our mutual understanding regarding amending
and supplementing the Agreement. Capitalized terms herein shall have the meaning
set forth in the Agreement. In consideration of our mutual obligations in this
Amendment and Supplement Letter, CNSI and Allergan hereby agree as follows:

         1.       EXTENSION OF RESEARCH PHASE. The Research Phase as described
in Section 1.31 of the Agreement shall be amended to have a term of four (4)
years, commencing November 20, 1996, and ending November 20, 2000. The Research
Phase will be subject to earlier termination as provided in the Agreement.
Attached to this Amendment and Supplement Letter as ANNEX A is the current
Research Plan. In consideration of CNSI's performance of its obligations for the
additional year of the Research Phase, Allergan will pay CNSI One Million Two
Hundred Fifty Thousand Dollars ($1,250,000), as supported by a Research Plan and
budget. The amount shall be payable as set forth in Section 9.1.1 of the
Agreement. In the event that Allergan terminates the Agreement pursuant to
Section 14.1 or 14.2, Allergan shall be obligated to pay, the unpaid portion, if
any, of such One Million Two Hundred and Fifty Thousand Dollars ($1,250,000), in
accordance with the payment schedule in Section 9.1.1 of the Agreement.

         2.       CHANGE IN AVAILABILITY PERIOD. Section 5.3 of the Agreement is
amended to change the definition of "Availability Period." From the date hereof,
Availability Period shall mean the period ending on the later of twelve (12)
months following the date of designation of an Active Compound as a
Collaboration Compound or May 20, 2000. In conformity with Section 5.3, CNSI
agrees that it will not grant any license or other rights to a Third Party under
its interest in any Collaboration Compound during the Availability Period. In
addition, the Availability Period may be extended pursuant to Section 5.3.

         3.       EXPANSION OF FIELD. For purposes of the research license in
Section 8.1.1 of the Agreement, the definition of Field shall be expanded to
mean research, development and commercialization activity with respect to
compounds which block one or more than one


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subclass of the glutamate-activated ion channels, including NMDA channels,
and/or one or more subclass of sodium channels, for the treatment of pain, in
addition to ophthalmic disease and disorders, provided however, that such
research license shall be nonexclusive outside the Field as originally defined
in the Agreement. The commercial license for any Development Compound and its
Back-Up Compounds selected by Allergan under Section 5.4, shall be exclusive in
the Field as expanded hereby. However, if Allergan designates a Collaboration
Compound as a Development Compound pursuant to Section 5.4 of the Agreement for
pain, and at that time Allergan has not designated that Collaboration Compound,
or another Collaboration Compound, as a Development Compound for the treatment
of ophthalmic diseases and disorders, then Allergan shall no longer have the
right to select a Development Compound for the treatment of ophthalmic diseases
and disorders.

         4.       MILESTONE PAYMENTS. The milestone payments set forth in
Section 9.4.1 of the Agreement shall be applicable only one time with respect to
each Development Compound (or its Back-Up Compounds) even if Allergan ultimately
reaches one or more of such milestones for more than one indication.

         5.       UPDATED LIST OF EXCLUDED COMPOUNDS. Prior to execution of this
Amendment and Supplement Letter, CNSI shall provide to Allergan an updated list
of Excluded Compounds as described in Section 5.7 of the Agreement. Such updated
list shall be attached to this amendment and supplement letter as ANNEX B.

         6.       PATENT PROSECUTION. The parties agree that, notwithstanding
anything in Section 10.2 of the Agreement to the contrary, patent applications
with respect to Joint Inventions or Joint Patent Rights, which have applications
with respect to a Development Compound whether inside the Field as originally
provided in the Agreement or as expanded under Section 3 of this Amendment and
Supplement Letter, shall be filed by Allergan in such countries as reasonably
determined by Allergan, after consultation with CNSI. Allergan shall consult
with CNSI as to the preparation and filing (if time permits), prosecution and
maintenance of such patent applications and patents, and shall furnish to CNSI
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 CNSI and Allergan shall seriously
consider all such comments. In the event that Allergan does not file, prosecute
and maintain any such patent application or patent as set forth above, it shall
give CNSI forty-five (45) days' notice before any relevant deadline and transmit
all information reasonable and appropriate relating to such patent application
or patent, and CNSI shall have the right to pursue, at its own expense, filing,
prosecution and maintenance thereof, in which event Allergan shall assign all
its rights therein to CNSI.

         7.       UPDATED REPRESENTATIONS AND WARRANTIES. Each party hereby
confirms to the other that as of the date hereof the representations and
warranties of such party in Article 12 of the Agreement are true and correct as
if made on the date hereof.

         8.       MODIFICATION OF TERMINATION PROVISION. Section 14.4.4 of the
Agreement entitled "Failure to Select a Development Compound" is hereby amended
to read "By either Party if Allergan has failed to select a Development Compound
pursuant to Section 5.4 by the fifth (5th) anniversary of the Effective Date."


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         9.       EFFECT OF TERMINATION. Section 14.2.3. of the Agreement,
entitled "Effect of Termination of Development Phase," is hereby amended to read
"In the event that Allergan delivers notice to CNSI pursuant to Section 14.2.1,
then (i) CNSI shall be free to grant a license to a Third Party for the use,
manufacture, distribution for sale and sale of such Development Compound or
Back-Up Compound for any indication, other than the treatment of (a) ophthalmic
diseases and disorders, and (b) pain, and (ii) the effects of termination set
forth under Section 14.6 hereof shall apply to such Development Compound or
Back-Up Compound."

         Except for the modifications and amendments set forth above, the
Agreement shall remain in full force and effect in accordance with its terms.

         In order to evidence your agreement with the foregoing, please sign
this letter where indicated below and return it to us.

                                 Very truly yours,


                                 ALLERGAN SALES, INC.


                                 /s/ George M. Lasezkay
                                 Corporate Vice President, Corporate Development


         Agreed to and acknowledged this 20th day of November, 1999.


                                 CAMBRIDGE NEUROSCIENCE, INC.


                                 /s/ Harry W. Wilcox
                                 President and Chief Executive Officer