Exhibit 4.2
                                                                -----------

                       FIRST AMENDMENT TO RIGHTS AGREEMENT


     FIRST  AMENDMENT,  dated  October  19,  2001  (this  "Amendment"),  between
Synaptic Pharmaceutical  Corporation, a Delaware corporation (the "Company") and
Mellon Investor Services LLC, a New Jersey Limited Liability  Company,  formerly
known as Chemical  Mellon  Shareholder  Services,  as rights  agent (the "Rights
Agent"),  to the Rights  Agreement,  dated as of December  11, 1995 (the "Rights
Agreement") between the Company and the Rights Agent.

     WHEREAS, the Company and the Rights Agent entered into the Rights Agreement
on December 11, 1995;

     WHEREAS,  the Company  represents and warrants that no "Distribution  Date"
has occurred as of the date hereof;

     WHEREAS,  the Company has determined  that the definition of  "Distribution
Date" in Section 1(j) of the Rights Agreement is defective,  in that it fails to
properly  provide  for the right of the  Board of  Directors  to  extend  when a
Distribution  Date  shall be deemed to have  occurred  to the 30th day after the
"Stock  Acquisition Date" or the date that a tender or exchange offer is made by
any person that would result in such person in becoming an  "Acquiring  Person,"
and

     WHEREAS,  pursuant  to and in  compliance  with  Section  27 of the  Rights
Agreement,  this  Amendment is being  entered into for purposes of setting forth
the corrected definition of "Distribution Date."

     NOW, THEREFORE,  in consideration of the premises and the mutual agreements
herein set forth, the parties hereto hereby agree as follows:

     All  capitalized  terms not otherwise  defined in this  Amendment  have the
respective meanings assigned thereto in the Rights Agreement.

     Section  1(j) of the  Rights  Agreement  is hereby  amended  to read in its
entirety by the following:

     "Distribution Date" shall mean (i) the earlier of (x) the close of business
on the tenth day after the Stock  Acquisition  Date (or,  if the tenth day after
the Stock  Acquisition Date occurs before the Record Date, the Close of Business
on the Record  Date),  or (y) the Close of  Business on the tenth  Business  Day
after the date that a tender or  exchange  offer by any  Person  (other  than an
Exempt  Person) is first  published  or sent or given within the meaning of Rule
14d-2(a) of the General  Rules and  Regulations  under the Exchange Act, if upon
consummation  thereof, such Person would be an Acquiring Person (irrespective of
whether any shares are  actually  purchased  pursuant to any such offer) or (ii)
such later date as the Board may determine in its sole  discretion but not later
than the 30th day  after the  Stock  Acquisition  Date or the 30th day after the
date a tender or exchange offer is first published, as the case may be."

     The term  "Agreement"  as used in the Rights  Agreement  shall be deemed to
refer to the Rights Agreement as amended hereby. The foregoing  amendments shall
be effective as of the date hereof and,  except as set forth herein,  the Rights
Agreement  shall  remain  in full  force  and  effect  and  shall  be  otherwise
unaffected hereby.

     This  Amendment  shall be governed by and construed in accordance  with the
laws of the State of Delaware.

     This Amendment may be executed in several counterparts, each of which shall
be an original,  but all of which  together  shall  constitute  one and the same
agreement.

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     IN WITNESS  WHEREOF,  the undersigned have caused this Amendment to be duly
exercised as of the day and year first above written.

                                  SYNAPTIC PHARMACEUTICAL CORPORATION

                                  By:/s/ Robert L. Spence
                                  -----------------------------------------
                                  Name:  Robert L. Spence
                                  Title:  Senior Vice President and CFO

                                  MELLON INVESTOR SERVICES LLC, as Rights Agent

                                  By:/s/ Jocelyn Montrose
                                  -----------------------------------------
                                  Name:  Jocelyn Montrose
                                  Title:  Relationship Manager