ISO Plan Option

                                 NONTRANSFERABLE
                        INCENTIVE STOCK OPTION AGREEMENT

                                       for

                                 Errol de Souza
                      -----------------------------------

     THIS AGREEMENT (this "Agreement"), dated as of September 9, 2002, is by and
between  SYNAPTIC  PHARMACEUTICAL   CORPORATION,  a  Delaware  corporation  (the
"Company"),  and Errol de Souza (the "Optionee," which term as used herein shall
be deemed to include  any  successor  to the  Optionee by will or by the laws of
descent and distribution, unless the context shall otherwise require).

                              W I T N E S S E T H:

     WHEREAS,  the  Company  and  the  Optionee  are  parties  to an  Employment
Agreement dated as of September 9, 2002 (the "Employment Agreement");

     WHEREAS,  the Employment  Agreement  provides for the grant of an option to
acquire 250,000 shares (the "Plan Option Shares") of the Company's  common stock
pursuant to the Synaptic  Pharmaceutical  Corporation  1996  Incentive Plan (the
"Plan"),  with such option to be treated as an  "incentive  stock option" to the
maximum extent permitted by law;

     WHEREAS,  based on the closing sale price of the Company's  common stock on
the Start Date (as defined below), no more than 69,565 of the Plan Option Shares
may be  subject  to an  incentive  stock  option  agreement  and this  agreement
provides an option for that number of shares;

     WHEREAS,  a separate  nonqualified  option  agreement is being entered into
between the Company and the Optionee to provide an option for the balance of the
Plan Option Shares; and

     WHEREAS, pursuant to the Plan, the Company, acting through the Compensation
Committee (the  "Committee") of its Board of Directors (the "Board"),  effective
September  9, 2002 (the  "Start  Date"),  granted to the  Optionee  an option to
purchase up to an aggregate of 69,565 shares of Common  Stock,  $0.01 par value,
of the  Company  (the  "Common  Stock"),  at the price of $5.75 per share,  such
option to be for the term and upon the terms and conditions hereinafter stated.

     NOW,  THEREFORE,  in  consideration of the mutual premises and undertakings
hereinafter set forth, the parties hereto agree as follows:

     1. Option;  Option  Price.  Pursuant to said action of the  Committee,  the
Company has granted to the Optionee the option (the "Option") to purchase,  upon
and  subject to the terms and  conditions  of this  Agreement  and the terms and
conditions  of the Plan (which are hereby  incorporated  by  reference  herein),
69,565 shares (the "Option  Shares") of Common Stock of the Company at the price
of $5.75 per share (the "Option Price"), which Option is intended to qualify for
Federal income tax purposes as an "incentive stock option" within the meaning of
Section 422 of the Internal Revenue Code of 1986, as amended (the "Code").

     2. Term.  The term (the "Option  Term") of the Option shall commence on the
Start Date and expire on the tenth  anniversary  of the Start  Date,  unless the
Option shall  theretofore  have been  terminated  in  accordance  with the terms
hereof or of the Plan.

     3. Exercisability; Time of Exercise.

     (a) General.  Unless  accelerated  in the discretion of the Committee or as
otherwise  provided herein,  the Option shall vest and become  exercisable as to
1/48th of the Option Shares each month,  commencing on the one-month anniversary
of the Start Date, so that the Option shall be vested and  exercisable as to all
of the Option Shares on the 48-month  anniversary  of the Start Date. The Option
shall  remain  exercisable  as to all shares as to which is  becomes  vested and
exercisable  until the  expiration  of the Option Term,  unless it is terminated
earlier as provided in any of the other  paragraphs of this Section 3 or Section
6 or as provided in the Plan.

     (b) Termination for Cause. If the Optionee shall cease to be an employee of
the  Company  as the  result  of a  Termination  for Cause  (as  defined  in the
Employment  Agreement),  the Option shall  automatically  terminate  on, and the
Optionee  shall have no further  right to exercise  the Option on or after,  the
date as of which  notice of such  termination  is given to the  Optionee  by the
Company.  As used in this  Agreement,  the term "Cause" has the meaning given to
such term in the Employment Agreement.

     (c)  Termination  Without  Cause;  Resignation  for  Good  Reason.  If  the
Optionee's   employment  with  the  Company   terminates  and  such  termination
constitutes a Termination Without Cause (as defined in the Employment Agreement)
or a Resignation for Good Reason (as defined in the Employment  Agreement),  the
vesting  of the  Option  shall  accelerate  so  that,  as of the  date  of  such
termination,  the Option shall be exercisable for the Option Shares, if any, for
which it has become  exercisable  pursuant to paragraph (a) of this Section 3 as
of the date of such termination plus an additional 24/48ths of the Option Shares
(up to the  total  number  of  Option  Shares).  The  Option  shall in any event
terminate  upon,  and the Optionee  shall have no further  right to exercise the
Option after,  the earlier of (i) the  expiration of the Option Term and (ii) 30
days after the date of such a termination.

     (d) Voluntary  Termination.  If the Optionee terminates his employment with
the Company by a Voluntary Termination (as defined in the Employment Agreement),
the Option shall be exercisable for the Option Shares,  if any, for which it has
become  exercisable  pursuant to paragraph  (a) of this Section 3 as of the date
the  Optionee  gives notice of such  termination.  The Option shall in any event
terminate  upon and the  Optionee  shall have no further  right to exercise  the
Option after,  the earlier of (i) the  expiration of the Option Term and (ii) 30
days after the date the Optionee gives notice of such termination.

     (e) Disability  Termination.  If the Optionee's employment with the Company
terminates and such termination constitutes a Disability Termination (as defined
in the  Employment  Agreement),  the vesting of the Option shall  accelerate  so
that, as of the date of such  termination,  the Option shall be exercisable  for
the Option  Shares,  if any,  for which it has become  exercisable  pursuant  to
paragraph  (a) of this  Section  3 as of the  date of such  termination  plus an
additional  12/48ths  of the  Option  Shares  (up to the total  number of Option
Shares).  The Option shall in any event  terminate  upon, and the Optionee shall
have no further  right to  exercise  the Option  after,  the  earlier of (i) the
expiration  of the  Option  Term  and (ii)  180  days  after  the date of such a
termination;  provided, however, that, in the case of any such termination other
than a  termination  resulting  from the Optionee  being  "disabled"  within the
meaning of Section  22(e)(3) of the Code,  the Option shall no longer be treated
as an  "incentive  stock  option"  within the meaning of Section 422 of the Code
unless exercised within three (3) months following the date of such termination.
For purposes of Agreement,  the term  "Disability"  has the meaning given to the
term "Employee's Disability" in the Employment Agreement.

     (f) Termination as a Result of Death. If the Optionee's employment with the
Company  terminates as a result of the Optionee's death, the Option shall, as of
the  date of such  termination,  be  exercisable  by the  Optionee's  Designated
Beneficiary  (as  defined  in the Plan) or  personal  representatives,  heirs or
legatees  (as  provided  in the  Plan),  and the  vesting  of the  Option  shall
accelerate  so that,  as of the date of such  termination,  the Option  shall be
exercisable for the Option Shares,  if any, for which it has become  exercisable
pursuant to paragraph  (a) of this Section 3 as of the date of such  termination
plus an  additional  12/48ths  of the Option  Shares (up to the total  number of
Option  Shares).  The Option shall in any event terminate upon, and the Optionee
(and the  Designated  Beneficiary)  shall have no further  right to exercise the
Option after,  the earlier of (i) the expiration of the Option Term and (ii) one
year after the date of death.  Notwithstanding anything contained in the Plan to
the contrary,  the Option shall  continue to be treated as an  "incentive  stock
option"  within  the  meaning  of  Section  422 of the  Code  even  if it is not
exercised  until  after the third  month  following  the date of the  Optionee's
death.

     (g) Death Following Disability. In the event of the Optionee's death within
180 days  following  a  Disability  Termination  (as  defined in the  Employment
Agreement),  the  Option  shall  thereafter  be  exercisable  by the  Optionee's
Designated  Beneficiary or personal  representatives,  heirs or legatees, to the
extent,  if any, which it shall have vested and become  exercisable  pursuant to
paragraphs  (a) and (d) of this Section 3 for a period of one (1) year following
the date of death but in no event later than the  expiration of the Option Term;
provided,  however,  that, in the case in which the  Optionee's  termination  of
employment  resulted from the Optionee  being  "disabled"  within the meaning of
Section  22(e)(3)  of the Code,  the  Option  shall no longer be  treated  as an
"incentive  stock  option"  within the meaning of Section 422 of the Code unless
exercised  within  one (1)  year  following  the date of such  termination;  and
provided further,  however, that, in all other cases, the Option shall no longer
be treated as an "incentive  stock option"  within the meaning of Section 422 of
the Code unless  exercised  within three (3) months  following  the date of such
termination.

     4.  Procedure for Exercise.  (a) The Option may be exercised,  from time to
time,  in whole or in part  (but for the  purchase  of whole  shares  only),  by
delivery of a written  notice (the  "Notice") from the Optionee to the Secretary
of the Company, which Notice shall:

     (i) state  that the  Optionee  elects to  exercise  the  Option  under this
Agreement;

     (ii)  state the number of shares  with  respect  to which the  Optionee  is
exercising the Option (the "Acquired Shares");

     (iii) include any  representations  of the Optionee  required under Section
7(b) hereof;

     (iv)  state the method of  payment  for the  Acquired  Shares  pursuant  to
Section 4(b);

     (v) in the event that the Option  shall be  exercised  by any person  other
than the Optionee pursuant to Sections 3 and 8, include appropriate proof of the
right of such person to exercise the Option; and

     (vi)  state the date upon which the  Optionee  desires  to  consummate  the
purchase of the Acquired  Shares (which date must be prior to the termination of
such Option).

     (b)  Payment of the Option  Price for the  Acquired  Shares  shall,  unless
otherwise  provided  by the  Committee,  be made (i) in cash or by  personal  or
certified  check,  or (ii) by delivery of shares of the  Company's  Common Stock
owned by the  Optionee  for more than six months  prior to the date of  exercise
having a value equal to the aggregate Option Price of the Acquired Shares,  with
such  delivered  shares to be valued at the closing sale price of the  Company's
Common  Stock on the Nasdaq  National  Market on the date of exercise  (provided
that, if the Company's Common Stock does not trade on the Nasdaq National Market
at such time, the value thereof shall be determined by the Committee in a manner
it deems appropriate).

     5. No Rights as a  Stockholder.  The Optionee shall not have any privileges
of a  stockholder  with  respect to any Option  Shares until the date of a stock
certificate representing such Option Shares is issued to the Optionee.

     6. Adjustments.

     (a) Stock Dividends,  Splits, Subdivisions or Combinations.  Subject to the
other  provisions  of this  Section  6, if,  at any time  while  the  Option  is
outstanding,  the  Common  Stock is changed  by reason of  dividends  payable in
Common Stock or splits,  subdivisions or combinations of shares of Common Stock,
then the  number  of  shares  of  Common  Stock  deliverable  upon the  exercise
thereafter of the Option shall be increased or decreased proportionately, as the
case may be, without change in the aggregate Option Price.

     (b) Cash Mergers.  Upon the occurrence of a merger on  consolidation of the
Company with another  corporation in a transaction in which the  stockholders of
the Company receive cash  consideration  in exchange for their shares of capital
stock  of  the  Company  (a  "cash  merger"),  the  Option  shall  automatically
terminate;  provided,  however,  that the  Optionee  shall be given (i)  written
notice of such cash merger at least 20 days prior to its proposed effective date
(as  specified  in such  notice)  and (ii) an  opportunity,  during  the  period
commencing  with  delivery of such notice and ending ten (10) days prior to such
proposed  effective date, to exercise the Option in full as to all of the Option
Shares, whether or not then vested.

     (c)  Assumption  or  Substitution  of  Options.   Notwithstanding  anything
contained  herein  or in the Plan to the  contrary,  Section  6(b)  shall not be
applicable if provision  shall be made in  connection  with such cash merger for
the  assumption  of the Option by, or the  substitution  for the Option of a new
option   covering  the  stock  of,  the   surviving,   successor  or  purchasing
corporation,  or a parent or subsidiary thereof, with appropriate adjustments as
to the number, kind and option price of shares subject to such option; provided,
however,  that the Board  shall,  to the extent not  inconsistent  with the best
interests  of the  Company  or  its  subsidiaries  (such  best  interests  to be
determined  in good faith by the Board,  in its sole  discretion),  use its best
efforts to ensure that any such assumption or substitution will not constitute a
modification,  extension or renewal of the Option  within the meaning of Section
424(h) of the Code and the regulations thereunder.

     (d) Corporate Transactions. Notwithstanding anything contained herein or in
the Plan to the contrary,  upon the occurrence of (i) a merger or  consolidation
of the Company  with another  corporation  in a  transaction  (other than a cash
merger) in which the  Company  shall not  survive or in which the Company is the
survivor but its capital stock is exchanged for stock,  securities,  or property
of another  entity or (ii) a sale of all or  substantially  all of the assets of
the Company (any  transaction  described in clause (i) or (ii) being referred to
herein as a "corporate transaction"), provision shall be made in connection with
such  corporate  transaction  for  the  assumption  of  the  Option  by,  or the
substitution  for  the  Option  of a new  option  covering  the  stock  of,  the
surviving,  successor  or  purchasing  corporation,  or a parent  or  subsidiary
thereof, with appropriate adjustments as to the number, kind and option price of
shares subject to such option;  provided,  however, that the Board shall, to the
extent  not  inconsistent  with  the  best  interests  of  the  Company  or  its
subsidiaries  (such best  interests to be determined in good faith by the Board,
in its sole discretion), use its best efforts to ensure that any such assumption
or substitution will not constitute a modification,  extension or renewal of the
Option  within the  meaning of  Section  424(h) of the Code and the  regulations
thereunder.

     (e)  Termination  Following a Change of Control.  Notwithstanding  anything
contained  herein or in the Plan to the  contrary,  in the event the  Optionee's
employment  with the Company or the person which is the surviving,  successor or
purchasing  corporation,  is  terminated  at any time  following  any  Change of
Control  (as  defined  in  the  Employment   Agreement)  and  such   termination
constitutes a Termination Without Cause (as defined in the Employment Agreement)
or a Resignation for Good Reason (as defined in the Employment  Agreement),  the
Option shall become exercisable in full as to all Option Shares,  whether or not
vested,  as of the date of such  termination,  and the  Optionee  shall have the
right to exercise  the Option as to any or all of such shares  until the earlier
of (i) the  expiration  of the Option Term and (ii) the 90th day  following  the
date of such termination, at which time the Option shall terminate.

     7.  Additional  Provisions  Related to  Exercise.  (a) The Option  shall be
exercisable  only on such  date or dates and  during  such  period  and for such
number of shares of Common Stock as are set forth in this Agreement.

     (b) To exercise the Option,  the Optionee  shall follow the  procedures set
forth in Section 4 hereof.  Upon the exercise of the Option as a time when there
is not in effect a registration  statement  under the Securities Act of 1933, as
amended,  relating to the shares of Common Stock  issuable  upon exercise of the
Option,  the Optionee  shall provide the Company with such  representations  and
warranties  as may be required by the  Committee to the effect that the Acquired
Shares are being acquired for investment and not with a view to the distribution
thereof. Anything contained herein to the contrary notwithstanding, in the event
the Board  shall  determine,  in its sole and  subjective  discretion,  that the
registration,  qualification  or listing of the Option  Shares upon a securities
exchange  or under any state or Federal  law,  or the consent or approval or any
government or regulatory body, is necessary or desirable as a condition of or in
connection with the exercise of the Option, the Option may not be exercised,  in
whole or in part, unless and until such  registration,  qualification,  listing,
consent or approval  shall have been effected or obtained free of any conditions
not acceptable to the Board.

     (c) The Option shall not be affected by any change of duties or position of
the  Optionee  (including  transfer  to or  from a  subsidiary),  so long as the
Optionee  continues to be an employee of the Company or one of its subsidiaries.
Nothing in the Option granted hereunder shall confer upon the Optionee any right
to continue in the employ of the Company or any of its subsidiaries or interfere
in any way with the right of the Company or its subsidiaries or the stockholders
of the Company, as the case may be, to terminate the Optionee's employment or to
increase or decrease the Optionee's compensation at any time.

     8.  Restriction on Transfer.  The Option may not be  transferred,  pledged,
assigned,  hypothecated  (whether by  operation  of law or  otherwise),  sold or
otherwise disposed of in any way by the Optionee,  except by will or by the laws
of descent and  distribution,  and may be  exercised  during the lifetime of the
Optionee only by the Optionee. If the Optionee dies, the Option shall thereafter
be  exercisable,  during the  applicable  period  specified in Section 3, by the
Optionee's Designated Beneficiary or personal representatives, heirs or legatees
(as provided in the Plan) to the full extent to which the Option was exercisable
by the  Optionee at the time of the  Optionee's  death as provided  herein.  The
Option shall not be subject to  execution,  attachment or similar  process.  Any
attempted transfer, pledge, assignment, hypothecation, sale or other disposition
of the Option contrary to the provisions  hereof, and the levy of any execution,
attachment  or  similar  process  upon  the  Option,  shall be null and void and
without effect.

     9.  Restrictive  Legends.  In  order to  reflect  certain  restrictions  on
disposition of the shares acquired upon exercise of the Option (the  "Restricted
Shares"), all stock certificates representing the Restricted Shares issued shall
have affixed thereto any legends determined by the Company to be appropriate.

     10.  Notices.  All notices or other  communications  which are  required or
permitted  hereunder  shall  be in  writing  and  sufficient  if (i)  personally
delivered or sent by telecopier,  (ii) sent by  nationally-recognized  overnight
courier or (iii) sent by registered or certified mail,  postage prepaid,  return
receipt requested, addressed as follows:

                  if to the Optionee, to:

                           Errol de Souza
                           c/o Synaptic Pharmaceutical Corporation
                           215 College Road
                           Paramus, New Jersey 07652

                  with a copy to:

                           Claude E. Johnston
                           Managing Partner
                           Pearl Meyer & Partners
                           445 Park Avenue
                           New York, NY 10022-2606

                  if to the Corporation, to:

                           Synaptic Pharmaceutical Corporation
                           215 College Road
                           Paramus, New Jersey 07652
                           Attention: President Telecopier: 201-261-0623

                  With a copy to:

                           Robert Murray, Esq.
                           Baker Botts L.L.P.
                           30 Rockefeller Plaza
                           New York, NY 10112

                           Stephen W. Skonieczny, Esq.
                           Dechert
                           30 Rockefeller Plaza
                           New York, NY 10112

     or to such  other  address  as the party to whom  notice is to be given may
have furnished to each other party in writing in accordance  herewith.  Any such
communication  shall  be  deemed  to have  been  given  (i) when  delivered,  if
personally  delivered,  sent by  telecopier  or  sent  by  nationally-recognized
overnight  courier and (ii) on the third Business Day (as  hereinafter  defined)
following the date on which the piece of mail containing such  communication  is
posted, if sent by mail. As used herein,  "Business Day" means a day that is not
a Saturday,  Sunday or a day on which banking  institutions in the city to which
the notice or communication is to be sent are not required to be open.

     11.  Disqualifying  Disposition.  If the Optionee disposes of any shares of
Common Stock acquired upon the exercise of the Option within two years after the
Start Date or within one year after such  shares were  acquired  pursuant to the
exercise of the Option, the Optionee shall notify the Company in writing of such
disposition. Any notice required under this Section shall be given within thirty
days of such disposition.

     12. No Waiver. No waiver of any breach or condition of this Agreement shall
be deemed to be a waiver of any other or subsequent breach or condition, whether
of like or different nature.

     13.  Optionee  Undertaking.  The Optionee  hereby  agrees to take  whatever
additional actions and execute whatever additional  documents the Company may in
its  reasonable  judgement  deem necessary or advisable in order to carry out or
effect one or more of the  obligations or  restrictions  imposed on the Optionee
pursuant to the express provisions of this Agreement.

     14.  Modification  of Rights.  The rights of the  Optionee  are  subject to
modification and termination in certain events as provided in this Agreement and
the Plan.

     15.  Governing Law. This  Agreement  shall be governed by, and construed in
accordance  with,  the laws of the State of New Jersey  without giving effect to
principles of conflicts of laws.

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

     17.  Entire  Agreement.  This  Agreement,  the  Employment  Agreement  (the
provisions of which related to stock options are hereby  incorporated  herein by
reference) and the Plan constitute the entire agreement between the parties with
respect to the subject  matter hereof and thereof,  and supersede all previously
written or oral negotiations,  commitments,  representations and agreements with
respect  thereto.  In the event of any  inconsistency  between the terms of this
Agreement and the terms of the Plan, the terms of the Plan shall control.





                            [Signature Page Follows]







<PAGE>



                  IN WITNESS WHEREOF, the parties hereto have executed this
Agreement as of the date first written above.

                                     SYNAPTIC PHARMACEUTICAL CORPORATION




                                     By:/s/ Jonathan Leff
                                        ---------------------------------
                                     Name:
                                     Title:




                                     OPTIONEE

                                     /s/ Errol B. De Souza
                                     ------------------------------------
                                         Errol de Souza