<PAGE>   1
                    As filed with the Securities and Exchange
                        Commission on December 4, 1996.

                                                          Registration No. 333 -
--------------------------------------------------------------------------------
                       SECURITIES AND EXCHANGE COMMISSION
                             Washington, D.C. 20549

                                    FORM S-8

                             REGISTRATION STATEMENT
                                      UNDER
                           THE SECURITIES ACT OF 1933

                          HOUGHTEN PHARMACEUTICALS INC.
                          -----------------------------
             (Exact name of registrant as specified in its charter)

           Delaware                                           51-0336233
------------------------------                    ------------------------------
 (State or other jurisdiction of                           (I.R.S. Employer
  incorporation or organization)                          Identification No.)

   3550 General Atomics Court
      San Diego, California                                     92121
------------------------------                    ------------------------------
      (Address of Principal                                   (Zip Code)
        Executive Offices)


                1995 STOCK PLAN OF HOUGHTEN PHARMACEUTICALS, INC.
         ---------------------------------------------------------------
                            (Full title of the plan)

                                                             Copy to:

     ROBERT S. WHITEHEAD                                  T. MICHAEL HIRD

Houghten Pharmaceuticals, Inc.                      Pillsbury Madison & Sutro
  3550 General Atomics Court                       101 W. Broadway, Suite 1800
San Diego, California 92121                         San Diego, California 92101
      (619) 455-2544                                      (619) 544-3176

------------------------------                    ------------------------------
 (Name, address and telephone
  number, including area code,
    of agent for service)

<TABLE>
<CAPTION>
                                                   CALCULATION OF REGISTRATION FEE
--------------------------------------------------------------------------------------------------------------------------------
           Title of                        Amount              Proposed Maximum            Proposed                 Amount of
         Securities To                      To Be               Offering Price         Maximum Aggregate          Registration
         Be Registered                   Registered              per Share(1)          Offering Price(1)               Fee
--------------------------------------------------------------------------------------------------------------------------------
<S>                                     <C>                         <C>                  <C>                         <C>    
         Common Stock,                  421,424 shares              $4.875               $2,054,442.00               $623.00
        par value $.001
</TABLE>


(1)        Pursuant to Rule 457(c) under the Securities Act of 1933, the
           registration fee is based upon the average of the high and low prices
           of the Common Stock as quoted on the Nasdaq National Market on
           November 27, 1996.

                                -----------------

           This Registration Statement shall become effective upon filing in
accordance with Rule 462 under the Securities Act of 1933.
--------------------------------------------------------------------------------
<PAGE>   2
                                     PART I

              INFORMATION REQUIRED IN THE SECTION 10(a) PROSPECTUS

Item 1.           Plan Information.*

Item 2.           Registrant Information and Employee Plan Annual
                  Information.*

*        Information required by Part I to be contained in the Section 10(a)
         prospectus is omitted from this Registration Statement in accordance
         with Rule 428 under the Securities Act of 1933, as amended (the "1933
         Act"), and the Note to Part I of Form S-8.

                                     PART II

               INFORMATION REQUIRED IN THE REGISTRATION STATEMENT

Item 3.           Incorporation of Certain Documents by Reference.

         The following documents filed by Registrant with the Securities and
Exchange Commission (the "SEC") are incorporated by reference in this
registration statement:

         (1)      Registrant's prospectus filed pursuant to Rule 424(b) under
                  the 1933 Act in connection with Registrant's registration
                  statement on Form S-1 (SEC file no. 333-1376).

         (2)      All reports filed by Registrant pursuant to Section 13(c) or
                  15(d) of the Securities Exchange Act of 1934, as amended (the
                  "1934 Act"), since December 31, 1995.

         (3)      The description of Registrant's Common Stock contained
                  in Registrant's registration statement on Form 8-A
                  filed on March 13, 1996.

         In addition, all documents subsequently filed by Registrant with the
SEC pursuant to Sections 13(a), 13(c), 14 and 15(d) of the 1934 Act prior to the
filing of a post-effective amendment which indicates that all securities offered
have been sold or which deregisters all securities then remaining unsold, shall
be deemed to be incorporated by reference in this registration statement and to
be a part hereof from the date of filing of such documents.

Item 4.           Description of Securities.

         Not applicable.


                                       -2-
<PAGE>   3
Item 5.           Interests of Named Experts and Counsel.

         Not applicable.

Item 6.           Indemnification of Directors and Officers.

         Section 145 of the Delaware General Corporation Law (the "DGCL")
provides for the indemnification of officers, directors and other corporate
agents in terms sufficiently broad to indemnify such persons under certain
circumstances for liabilities (including reimbursement of expenses incurred)
arising under the 1933 Act. Article VII of the Registrant's Restated Certificate
of Incorporation provides for indemnification to the fullest extent authorized
by the DGCL. The Registrant has also entered into agreements with each of its
directors that provide for the indemnification of and the advancement of
expenses to such persons to the greatest extent permitted by Delaware law.

Item 7.           Exemption from Registration Claimed.

         Not applicable.

Item 8.           Exhibits.

         See Index to Exhibits.

Item 9.           Undertakings.

         (a)  The undersigned Registrant hereby undertakes:

                  (1) To file, during any period in which offers or sales are
         being made, a post-effective amendment to this registration statement:

                           (i)  To include any prospectus required by
                  Section 10(a)(3) of the Securities Act of 1933.

                           (ii) To reflect in the prospectus any facts or events
                  arising after the effective date of the registration statement
                  (or the most recent post-effective amendment thereof) which,
                  individually or in the aggregate, represent a fundamental
                  change in the information set forth in the registration
                  statement. Notwithstanding the foregoing, any increase or
                  decrease in volume of securities offered (if the total dollar
                  value of securities offered would not exceed that which was
                  registered) and any deviation from the low or high and of the
                  estimated maximum offering range may be reflected in the form
                  of prospectus filed with the Commission pursuant to Rule
                  424(b) if, in the aggregate, the changes in volume and price


                                       -3-
<PAGE>   4
                  represent no more than 20 percent change in the maximum
                  aggregate offering price set forth in the "Calculation of
                  Registration Fee" table in the effective registration
                  statement.

                           (iii) To include any material information with
                  respect to the plan of distribution not previously disclosed
                  in the registration statement or any material change to such
                  information in the registration statement.

         Provided, however, that paragraphs (a)(1)(i) and (a)(1)(ii) do not
         apply if the registration statement is on Form S-3 or Form S-8, and the
         information required to be included in a post-effective amendment by
         those paragraphs is contained in periodic reports filed by the
         Registrant pursuant to section 13 or section 15(d) of the Securities
         Exchange Act of 1934 that are incorporated by reference in the
         registration statement.

                  (2) That, for the purpose of determining any liability under
         the Securities Act of 1933, each such post-effective amendment shall be
         deemed to be a new registration statement relating to the securities
         offered therein, and the offering of such securities at that time shall
         be deemed to be the initial bona fide offering thereof.

                  (3) To remove from registration by means of a post-effective
         amendment any of the securities being registered which remain unsold at
         the termination of the offering.

                  (b) The undersigned Registrant hereby further undertakes that,
for purposes of determining any liability under the Securities Act of 1933, each
filing of the Registrant's annual report pursuant to Section 13(a) or 15(d) of
the Securities Exchange Act of 1934 that is incorporated by reference in the
registration statement shall be deemed to be a new registration statement
relating to the securities offered therein, and the offering of such securities
at that time shall be deemed to be the initial bona fide offering thereof.

                  (c) Insofar as indemnification for liabilities arising under
the Securities Act of 1933 may be permitted to directors, officers and
controlling persons of the Registrant pursuant to the foregoing provisions, or
otherwise, the Registrant has been advised that in the opinion of the Securities
and Exchange Commission such indemnification is against public policy as
expressed in the Act and is, therefore, unenforceable. In the event that a claim
for indemnification against such liabilities (other than the payment by the


                                       -4-
<PAGE>   5
Registrant of expenses incurred or paid by a director, officer or controlling
person of the Registrant in the successful defense of any action, suit or
proceeding) is asserted by such director, officer or controlling person in
connection with the securities being registered, the Registrant will, unless in
the opinion of its counsel the matter has been settled by controlling precedent,
submit to a court of appropriate jurisdiction the question whether such
indemnification by it is against public policy as expressed in the Act and will
be governed by the final adjudication of such issue.


                                       -5-
<PAGE>   6
                                   SIGNATURES

         Pursuant to the requirements of the Securities Act of 1933, the
Registrant certifies that it has reasonable grounds to believe that it meets all
of the requirements for filing on Form S-8 and has duly caused this registration
statement to be signed on its behalf by the undersigned, thereunto duly
authorized, in the City of San Diego, State of California, on December 2, 1996.

                                           HOUGHTEN PHARMACEUTICALS, INC.


                                           By */s/ Robert S. Whitehead
                                              ------------------------------
                                               Robert S. Whitehead
                                           President and Chief Executive Officer
                                          (Principal Executive Officer)

         Pursuant to the requirements of the Securities Act of 1933, this
registration statement has been signed by the following persons in the
capacities and on the date indicated:

<TABLE>
<CAPTION>
Name                                       Title                                          Date
----                                       -----                                          ----

<S>                                      <C>                                             <C>
*/s/ Robert S. Whitehead                 President and Chief Executive                   December 2, 1996
--------------------------------------   Officer (Principal Executive
     Robert S. Whitehead                 Officer) and Director       
                                         

 /s/ Terence E. McMorrow                 Vice President, Finance and                     December 2, 1996
--------------------------------------   Corporate Development (Principal 
     Terence E. McMorrow                 Financial and Accounting Officer)
                                         

 /s/ Richard A. Houghten                 Chief Scientific Officer and                    December 2, 1996
--------------------------------------   Director
     Richard A. Houghten               


*/s/ James C. Blair                      Chairman of the Board of                        December 2, 1996
--------------------------------------   Directors
     James C. Blair               


*/s/ William T. Comer                    Director                                        December 2, 1996
--------------------------------------
     William T. Comer
</TABLE>


                                       -6-
<PAGE>   7
<TABLE>
<CAPTION>
Name                                   Title                         Date
----                                   -----                         ----

<S>                                   <C>                       <C>
*/s/ Gregory J. Forrest               Director                  December 2, 1996
--------------------------------
     Gregory J. Forrest

                                      Director
--------------------------------
     Cam L. Garner


*/s/ Harry D. Lambert                 Director                  December 2, 1996
--------------------------------
     Harry D. Lambert

*/s/ Harvey S. Sadow                  Director                  December 2, 1996
--------------------------------
     Harvey S. Sadow

                                      Director
--------------------------------
     Ronald R. Tuttle

*  By  /s/ Terence E. McMorrow
       -------------------------
       Attorney-in-fact
</TABLE>


                                       -7-
<PAGE>   8
                                INDEX TO EXHIBITS

<TABLE>
<CAPTION>
Exhibit                                                                      Sequentially
Number                Exhibit                                                Numbered Page
------                -------                                                -------------

<S>                   <C>                                                          <C>  
4.1                   Form of Restated Certificate of                              *
                      Incorporation of Registrant.

4.2                   Amended and Restated Bylaws of                               *
                      Registrant.

5.1                   Opinion regarding legality of                                9
                      securities to be offered.

10.1                  1995 Stock Plan of Houghten
                      Pharmaceuticals, Inc.                                        *

23.1                  Consent of Ernst & Young LLP,                                10
                      Independent Auditors.

23.2                  Consent of Pillsbury Madison &                               --
                      Sutro (included in Exhibit 5.1).

24.1                  Power of Attorney.                                           11
</TABLE>

----------------

*        Exhibits 4.1, 4.2 and 10.1 are incorporated by reference to Exhibits
         3.3, 3.5 and 10.5, respectively, to Registrant's registration statement
         on Form S-1 (SEC file no. 333-1376) filed on February 14, 1996.

                                                    
                                      -8-
[{"type": "S-8", "sequence": "1", "description": "FORM S-8", "secsgml_size_bytes": 16887}]
{"company-data": {"conformed-name": "HOUGHTEN PHARMACEUTICALS INC", "cik": "0000887920", "assigned-sic": "2836", "irs-number": "510336233", "state-of-incorporation": "DE", "fiscal-year-end": "1231"}, "filing-values": {"form-type": "S-8", "act": "33", "file-number": "333-17273", "film-number": "96676020"}, "business-address": {"street1": "3550 GENERAL ATOMICS COURT", "city": "SAN DIEGO", "state": "CA", "zip": "92121", "phone": "6194553814"}, "mail-address": {"street1": "3550 GENERAL ATOMICS COURT", "street2": "3550 GENERAL ATOMICS COURT", "city": "SANSAN DIEGO", "state": "CA", "zip": "92121"}}
1
                    As filed with the Securities and Exchange
                        Commission on December 4, 1996.

                                                          Registration No. 333 -
--------------------------------------------------------------------------------
                       SECURITIES AND EXCHANGE COMMISSION
                             Washington, D.C. 20549

                                    FORM S-8

                             REGISTRATION STATEMENT
                                      UNDER
                           THE SECURITIES ACT OF 1933

                          HOUGHTEN PHARMACEUTICALS INC.
                          -----------------------------
             (Exact name of registrant as specified in its charter)

           Delaware                                           51-0336233
------------------------------                    ------------------------------
 (State or other jurisdiction of                           (I.R.S. Employer
  incorporation or organization)                          Identification No.)

   3550 General Atomics Court
      San Diego, California                                     92121
------------------------------                    ------------------------------
      (Address of Principal                                   (Zip Code)
        Executive Offices)

                1995 STOCK PLAN OF HOUGHTEN PHARMACEUTICALS, INC.
         ---------------------------------------------------------------
                            (Full title of the plan)

                                                             Copy to:

     ROBERT S. WHITEHEAD                                  T. MICHAEL HIRD

Houghten Pharmaceuticals, Inc.                      Pillsbury Madison & Sutro
  3550 General Atomics Court                       101 W. Broadway, Suite 1800
San Diego, California 92121                         San Diego, California 92101
      (619) 455-2544                                      (619) 544-3176

------------------------------                    ------------------------------
 (Name, address and telephone
  number, including area code,
    of agent for service)
CALCULATION OF REGISTRATION FEE
--------------------------------------------------------------------------------------------------------------------------------
           Title of                        Amount              Proposed Maximum            Proposed                 Amount of
         Securities To                      To Be               Offering Price         Maximum Aggregate          Registration
         Be Registered                   Registered              per Share(1)          Offering Price(1)               Fee
--------------------------------------------------------------------------------------------------------------------------------
Common Stock,                  421,424 shares              $4.875               $2,054,442.00               $623.00
        par value $.001
(1)        Pursuant to Rule 457(c) under the Securities Act of 1933, the
           registration fee is based upon the average of the high and low prices
           of the Common Stock as quoted on the Nasdaq National Market on
           November 27, 1996.

                                -----------------

           This Registration Statement shall become effective upon filing in
accordance with Rule 462 under the Securities Act of 1933.
--------------------------------------------------------------------------------
2
                                     PART I

              INFORMATION REQUIRED IN THE SECTION 10(a) PROSPECTUS

Item 1.           Plan Information.*

Item 2.           Registrant Information and Employee Plan Annual
                  Information.*

*        Information required by Part I to be contained in the Section 10(a)
         prospectus is omitted from this Registration Statement in accordance
         with Rule 428 under the Securities Act of 1933, as amended (the "1933
         Act"), and the Note to Part I of Form S-8.

                                     PART II

               INFORMATION REQUIRED IN THE REGISTRATION STATEMENT

Item 3.           Incorporation of Certain Documents by Reference.

         The following documents filed by Registrant with the Securities and
Exchange Commission (the "SEC") are incorporated by reference in this
registration statement:

         (1)      Registrant's prospectus filed pursuant to Rule 424(b) under
                  the 1933 Act in connection with Registrant's registration
                  statement on Form S-1 (SEC file no. 333-1376).

         (2)      All reports filed by Registrant pursuant to Section 13(c) or
                  15(d) of the Securities Exchange Act of 1934, as amended (the
                  "1934 Act"), since December 31, 1995.

         (3)      The description of Registrant's Common Stock contained
                  in Registrant's registration statement on Form 8-A
                  filed on March 13, 1996.

         In addition, all documents subsequently filed by Registrant with the
SEC pursuant to Sections 13(a), 13(c), 14 and 15(d) of the 1934 Act prior to the
filing of a post-effective amendment which indicates that all securities offered
have been sold or which deregisters all securities then remaining unsold, shall
be deemed to be incorporated by reference in this registration statement and to
be a part hereof from the date of filing of such documents.

Item 4.           Description of Securities.

         Not applicable.

                                       -2-
3
Item 5.           Interests of Named Experts and Counsel.

         Not applicable.

Item 6.           Indemnification of Directors and Officers.

         Section 145 of the Delaware General Corporation Law (the "DGCL")
provides for the indemnification of officers, directors and other corporate
agents in terms sufficiently broad to indemnify such persons under certain
circumstances for liabilities (including reimbursement of expenses incurred)
arising under the 1933 Act. Article VII of the Registrant's Restated Certificate
of Incorporation provides for indemnification to the fullest extent authorized
by the DGCL. The Registrant has also entered into agreements with each of its
directors that provide for the indemnification of and the advancement of
expenses to such persons to the greatest extent permitted by Delaware law.

Item 7.           Exemption from Registration Claimed.

         Not applicable.

Item 8.           Exhibits.

         See Index to Exhibits.

Item 9.           Undertakings.

         (a)  The undersigned Registrant hereby undertakes:

                  (1) To file, during any period in which offers or sales are
         being made, a post-effective amendment to this registration statement:

                           (i)  To include any prospectus required by
                  Section 10(a)(3) of the Securities Act of 1933.

                           (ii) To reflect in the prospectus any facts or events
                  arising after the effective date of the registration statement
                  (or the most recent post-effective amendment thereof) which,
                  individually or in the aggregate, represent a fundamental
                  change in the information set forth in the registration
                  statement. Notwithstanding the foregoing, any increase or
                  decrease in volume of securities offered (if the total dollar
                  value of securities offered would not exceed that which was
                  registered) and any deviation from the low or high and of the
                  estimated maximum offering range may be reflected in the form
                  of prospectus filed with the Commission pursuant to Rule
                  424(b) if, in the aggregate, the changes in volume and price

                                       -3-
4
                  represent no more than 20 percent change in the maximum
                  aggregate offering price set forth in the "Calculation of
                  Registration Fee" table in the effective registration
                  statement.

                           (iii) To include any material information with
                  respect to the plan of distribution not previously disclosed
                  in the registration statement or any material change to such
                  information in the registration statement.

         Provided, however, that paragraphs (a)(1)(i) and (a)(1)(ii) do not
         apply if the registration statement is on Form S-3 or Form S-8, and the
         information required to be included in a post-effective amendment by
         those paragraphs is contained in periodic reports filed by the
         Registrant pursuant to section 13 or section 15(d) of the Securities
         Exchange Act of 1934 that are incorporated by reference in the
         registration statement.

                  (2) That, for the purpose of determining any liability under
         the Securities Act of 1933, each such post-effective amendment shall be
         deemed to be a new registration statement relating to the securities
         offered therein, and the offering of such securities at that time shall
         be deemed to be the initial bona fide offering thereof.

                  (3) To remove from registration by means of a post-effective
         amendment any of the securities being registered which remain unsold at
         the termination of the offering.

                  (b) The undersigned Registrant hereby further undertakes that,
for purposes of determining any liability under the Securities Act of 1933, each
filing of the Registrant's annual report pursuant to Section 13(a) or 15(d) of
the Securities Exchange Act of 1934 that is incorporated by reference in the
registration statement shall be deemed to be a new registration statement
relating to the securities offered therein, and the offering of such securities
at that time shall be deemed to be the initial bona fide offering thereof.

                  (c) Insofar as indemnification for liabilities arising under
the Securities Act of 1933 may be permitted to directors, officers and
controlling persons of the Registrant pursuant to the foregoing provisions, or
otherwise, the Registrant has been advised that in the opinion of the Securities
and Exchange Commission such indemnification is against public policy as
expressed in the Act and is, therefore, unenforceable. In the event that a claim
for indemnification against such liabilities (other than the payment by the

                                       -4-
5
Registrant of expenses incurred or paid by a director, officer or controlling
person of the Registrant in the successful defense of any action, suit or
proceeding) is asserted by such director, officer or controlling person in
connection with the securities being registered, the Registrant will, unless in
the opinion of its counsel the matter has been settled by controlling precedent,
submit to a court of appropriate jurisdiction the question whether such
indemnification by it is against public policy as expressed in the Act and will
be governed by the final adjudication of such issue.

                                       -5-
6
                                   SIGNATURES

         Pursuant to the requirements of the Securities Act of 1933, the
Registrant certifies that it has reasonable grounds to believe that it meets all
of the requirements for filing on Form S-8 and has duly caused this registration
statement to be signed on its behalf by the undersigned, thereunto duly
authorized, in the City of San Diego, State of California, on December 2, 1996.

                                           HOUGHTEN PHARMACEUTICALS, INC.

                                           By */s/ Robert S. Whitehead
                                              ------------------------------
                                               Robert S. Whitehead
                                           President and Chief Executive Officer
                                          (Principal Executive Officer)

         Pursuant to the requirements of the Securities Act of 1933, this
registration statement has been signed by the following persons in the
capacities and on the date indicated:
Name                                       Title                                          Date
----                                       -----                                          ----
*/s/ Robert S. Whitehead                 President and Chief Executive                   December 2, 1996
--------------------------------------   Officer (Principal Executive
     Robert S. Whitehead                 Officer) and Director       
                                         

 /s/ Terence E. McMorrow                 Vice President, Finance and                     December 2, 1996
--------------------------------------   Corporate Development (Principal 
     Terence E. McMorrow                 Financial and Accounting Officer)
                                         

 /s/ Richard A. Houghten                 Chief Scientific Officer and                    December 2, 1996
--------------------------------------   Director
     Richard A. Houghten               

*/s/ James C. Blair                      Chairman of the Board of                        December 2, 1996
--------------------------------------   Directors
     James C. Blair               

*/s/ William T. Comer                    Director                                        December 2, 1996
--------------------------------------
     William T. Comer
-6-
7
Name                                   Title                         Date
----                                   -----                         ----
*/s/ Gregory J. Forrest               Director                  December 2, 1996
--------------------------------
     Gregory J. Forrest

                                      Director
--------------------------------
     Cam L. Garner

*/s/ Harry D. Lambert                 Director                  December 2, 1996
--------------------------------
     Harry D. Lambert

*/s/ Harvey S. Sadow                  Director                  December 2, 1996
--------------------------------
     Harvey S. Sadow

                                      Director
--------------------------------
     Ronald R. Tuttle

*  By  /s/ Terence E. McMorrow
       -------------------------
       Attorney-in-fact
-7-
8
                                INDEX TO EXHIBITS
Exhibit                                                                      Sequentially
Number                Exhibit                                                Numbered Page
------                -------                                                -------------
4.1                   Form of Restated Certificate of                              *
                      Incorporation of Registrant.

4.2                   Amended and Restated Bylaws of                               *
                      Registrant.

5.1                   Opinion regarding legality of                                9
                      securities to be offered.

10.1                  1995 Stock Plan of Houghten
                      Pharmaceuticals, Inc.                                        *

23.1                  Consent of Ernst & Young LLP,                                10
                      Independent Auditors.

23.2                  Consent of Pillsbury Madison &                               --
                      Sutro (included in Exhibit 5.1).

24.1                  Power of Attorney.                                           11
----------------

*        Exhibits 4.1, 4.2 and 10.1 are incorporated by reference to Exhibits
         3.3, 3.5 and 10.5, respectively, to Registrant's registration statement
         on Form S-1 (SEC file no. 333-1376) filed on February 14, 1996.

                                                    
                                      -8-