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                                                                   EXHIBIT 10.18

                               FIRST AMENDMENT TO
                              EMPLOYMENT AGREEMENT

         This First Amendment to Employment Agreement (the "First Amendment") is
executed and dated effective as of the 19th day of January, 2001 between
Zonagen, Inc. (the "Company") and Paul Lammers, M.D., M.Sc. (the "Executive").

         WHEREAS, the Company and Executive entered into an Employment Agreement
dated as of April 20, 1998 (the "Employment Agreement") which Employment
Agreement has been renewed pursuant to the terms thereof;

         WHEREAS, the Company and Executive now wish to amend certain provisions
of the Employment Agreement;

         NOW THEREFORE, in consideration of the foregoing and the mutual
covenants herein, the parties hereto agree as follows:

         1. Capitalized terms used but not defined herein have the respective
meanings set forth in the Employment Agreement.

         2. Section 3 of the Employment Agreement is hereby amended to include
the following paragraph:

                  "(ii)    Upon the earlier of (x) a Change of Control (as
                           defined below) of the Company or (y) the termination
                           of further action by the Board of Directors in
                           furtherance of a Change of Control, provided the
                           Executive is an employee of the Company on either
                           such date, the Executive shall receive a lump sum
                           bonus payment in the amount of $40,000, subject only
                           to such payroll and withholding deductions as are
                           required by applicable federal and state laws."

         3. Section 6 of the Employment Agreement is hereby amended to include
the following subsection (g) at the end thereof:

                  "Notwithstanding anything in this Section 6 to the contrary,
                  upon a Change of Control (as defined below), provided the
                  Executive is an employee of the Company immediately prior
                  thereto, the Company shall:

                           (i)      pay to the Executive, upon the closing of
                                    the Change of Control, a lump sum cash
                                    payment equal to .5 times the Executive's
                                    then current annual salary; such payment
                                    shall be in lieu of any other payments
                                    payable to the Executive pursuant to Section
                                    6(a) above, and the terms of Section 6(d)
                                    and 6(f) shall not apply in such instance;

                           (ii)     accelerate in full the vesting of all shares
                                    subject to any of the Executive's
                                    outstanding stock options, and Executive
                                    shall have a period of two years following
                                    the Change of Control to exercise such
                                    options; and

                           (iii)    continue, for the period of six (6) months
                                    commencing on the date of such Change of
                                    Control, to provide the benefits

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                                    contemplated by Section 4(a) of this
                                    Agreement (provided that the continuation of
                                    such benefits shall be construed so as not
                                    to extend the period during which the
                                    Company shall be required to provide
                                    benefits under COBRA following the date of
                                    such Change of Control).

                  As used in this Agreement, a "Change of Control" shall mean:

                           (i)      the acquisition after the Effective Date of
                                    this First Amendment, by any individual,
                                    entity or group (within the meaning of
                                    Section 13(d)(3) or 14(d)(2) of the
                                    Securities Exchange Act of 1934, as amended)
                                    (a "Person") of beneficial ownership of 30%
                                    or more of either (i) the then outstanding
                                    shares of common stock of the Company (the
                                    "Outstanding Common Stock") or (ii) the
                                    combined voting power of the then
                                    outstanding voting securities of the Company
                                    entitled to vote generally in the election
                                    of directors (the "Outstanding Voting
                                    Securities"), provided that for purposes of
                                    this subsection (i), the following
                                    acquisitions shall not constitute a Change
                                    of Control: (A) any acquisition directly
                                    from the Company, (B) any acquisition by the
                                    Company, (C) any acquisition by any employee
                                    benefit plan (or related trust) sponsored or
                                    maintained by the Company or any corporation
                                    controlled by the Company, or (D) any
                                    acquisition by any corporation pursuant to a
                                    transaction which complies with clauses (A),
                                    (B) and (C) of subsection (ii) hereof; or

                           (ii)     consummation after the Effective Date of
                                    this First Amendment of a reorganization,
                                    merger or consolidation or sale or other
                                    disposition of all or substantially all of
                                    the assets of the Company (a "Corporate
                                    Transaction") in each case, unless,
                                    following such Corporate Transaction, (A)
                                    (1) all or substantially all of the persons
                                    who were the beneficial owners of the
                                    Outstanding Common Stock immediately prior
                                    to such Corporate Transaction beneficially
                                    own, directly or indirectly, more than 30%
                                    of the then outstanding shares of common
                                    stock of the corporation resulting from such
                                    Corporate Transaction, and (2) all or
                                    substantially all of the persons who were
                                    the beneficial owners of the Outstanding
                                    Voting Securities immediately prior to such
                                    Corporate Transaction beneficially own,
                                    directly or indirectly, more than 30% of the
                                    combined voting power of the then
                                    outstanding voting securities entitled to
                                    vote generally in the election of directors
                                    of the corporation resulting from such
                                    Corporate Transaction (including, without
                                    limitation, a corporation which as a result
                                    of such transaction owns the Company or all
                                    or substantially all of the Company's assets
                                    either directly or through one or more
                                    subsidiaries) in substantially the same
                                    proportions as their ownership of the

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                                    Outstanding Common Stock and the Outstanding
                                    Voting Securities immediately prior to such
                                    Corporate Transaction, as the case may be,
                                    (B) no Person (excluding (l) any corporation
                                    resulting from such Corporate Transaction or
                                    any employee benefit plan (or related trust)
                                    of the Company or such corporation resulting
                                    from such Corporate Transaction and (2) any
                                    Person approved by the members of the Board
                                    in office immediately prior to such
                                    Corporate Transaction) beneficially owns,
                                    directly or indirectly, 30% or more of the
                                    then outstanding shares of common stock of
                                    the corporation resulting from such
                                    Corporate Transaction or the combined voting
                                    power of the then outstanding voting
                                    securities of such corporation except to the
                                    extent that such ownership existed prior to
                                    such Corporate Transaction and (C) at least
                                    a majority of the members of the board of
                                    directors of the corporation resulting from
                                    such Corporate Transaction were members of
                                    the Board at the time of the execution of
                                    the initial agreement or of the action of
                                    the Board providing for such Corporate
                                    Transaction."

         4. In addition, and notwithstanding any other provision of his
Employment Agreement to the contrary, Executive shall be permitted to consult
with other companies during the term of this Employment Agreement, provided that
such consulting activities do not interfere with Employee's duties to the
Company or otherwise violate the terms of the Proprietary Information and
Inventions and Non-Competition Agreement entered into between the Company and
Executive, and are conducted on Executive's own time. Further, Executive shall
be permitted to have reasonable use of Company facilities (telephone, computers,
fax) during his employment term to pursue other employment opportunities,
provided that such use does not interfere with the discharge of his employment
duties to the Company.

         5. Except as amended and modified by this First Amendment, the
Employment Agreement shall continue in full force and effect. The Employment
Agreement and this First Amendment shall be construed as one and the same
instrument.

         6. This First Amendment may be signed in any number of counterparts,
each of which shall be deemed an original, but all of which together shall
constitute one and the same instrument, and it shall not be necessary in making
proof of this First Amendment to produce or account for more than one such
counterpart.

         7. This First Amendment (i) constitutes the entire contract between the
parties relative to the amendments to the Employment Agreement made hereby, (ii)
supersedes all prior agreements, consents and undertakings relating to such
amendments and (iii) may not be contradicted by evidence of prior
contemporaneous or subsequent oral agreements of the parties.

         8. This First Amendment shall be construed and enforced in accordance
with the laws of the State of Texas.

         9. This First Amendment shall be binding upon and shall inure to the
benefit of and enforceable by the parties hereto and their respective successors
and assigns.

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         IN WITNESS WHEREOF, the parties have executed this First Amendment to
the Employment Agreement effective (the "Effective Date") for all purposes as of
the date first above written.

EMPLOYEE                                            COMPANY

                                                    ZONAGEN, INC.

/s/    Paul Lammers                                 By: /s/ Joseph S. Podolski
------------------------------------                   -------------------------
Paul Lammers, M.D., M.Sc.                              Joseph S. Podolski
                                                       President and
                                                       Chief Executive Officer

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                                                                   EXHIBIT 10.21

                                 FIRST AMENDMENT
                                     TO THE
                                  ZONAGEN, INC.
                 2000 NON-EMPLOYEE DIRECTORS' STOCK OPTION PLAN

         This First Amendment to the Zonagen, Inc. (the "Company") 2000
Non-Employee Directors' Stock Option Plan (the "Amendment") is executed pursuant
to Section 12 of the Company's 2000 Non-Employee Directors' Stock Option Plan
(the "Plan"). All capitalized and undefined terms used herein shall have the
meanings ascribed to such terms in the Plan.

         WHEREAS, the Company's Board of Directors (the "Board") is authorized
by Section 12 of the Plan to amend the Plan from time to time, subject to any
required stockholder approval of any such amendments; and

         WHEREAS, the Board desires to amend the Plan, effective as of May 23,
2000, to allow for issuance of stock awards and options under the Plan in order
to allow the Company to pay fees owed to directors and consultants in stock
awards and options in lieu of cash; and

         WHEREAS, such amendments do not require stockholder approval as set
forth in Section 12 of the Plan.

         NOW, THEREFORE, in connection with the foregoing, the Plan is hereby
amended as follows:

         1. The following is hereby inserted as a new Section 7 of the Plan, and
the original Section 7 and subsequent sections under the Plan are accordingly
renumbered:

                  "7. DIRECTOR FEES

                           (a) PER-MEETING FEE. The Company shall pay each
                  Non-Employee Director One Thousand Dollars ($1,000) (the
                  "Director Fee") in (x) cash, (y) shares of Common Stock; or
                  (z) an Option (the "Director Fee Option") to purchase shares
                  of Common Stock, at his or her election, for each meeting of
                  the Board at which he or she attends in person. The Director
                  Fee is payable on the date which the meeting is held. If a
                  Non-Employee Director elects to receive Common Stock or an
                  Option, the number of shares to be granted pursuant to this
                  Section 7(a) shall be determined in accordance with the
                  following:

                                    (i) the number of shares of Common Stock to
                           be delivered pursuant to Section 7(a) shall be
                           determined by dividing (x) the Director Fee by (y)
                           the Fair Market Value of a share of Common Stock on
                           the date such award is payable; and

                                    (ii) the number of shares granted pursuant
                           to the Director Fee Option to be delivered pursuant
                           to Section 7(a) shall be determined by dividing (x)
                           the Director Fee by (y) the Fair Market Value of a
                           share of Common Stock on the date such award is
                           payable and (z) multiplying the quotient by two (2);
                           further, the Director Fee Option will be immediately
                           exercisable;

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                           (b) STOCK CERTIFICATE. Each Non-Employee Director
                  electing to receive the Director Fee in Common Stock shall be
                  issued a stock certificate in his or her name and shall bear
                  an appropriate restrictive legend."

         2. Except as amended hereby, the terms and provisions of the Plan shall
remain in full force and effect, and the Plan and this Amendment shall be read,
taken and construed as one and the same instrument.

         IN WITNESS WHEREOF, and as conclusive evidence of the adoption and
approval of the foregoing First Amendment to the Plan by the Board, the Company
has caused this Amendment to be duly executed in its name and behalf by its
proper officers thereunto duly authorized as of the 23rd day of May, 2000.

                                    ZONAGEN, INC.

                                    By: /s/ Joseph S. Podolski
                                        ----------------------------------------
                                    Name: Joseph S. Podolski
                                          --------------------------------------
                                    Title: President & CEO
                                           -------------------------------------

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