<PAGE>   1
                                  EXHIBIT 10.46

            AMENDMENT TO THE SENIOR LINE OF CREDIT AGREEMENT AND NOTES


      This is an Amendment to the Senior Line of Credit Agreement between Aries
Domestic Fund, the Aries Fund, a Cayman Islands Trust (the "Funds"), and
Xenometrix, Inc. (the "Company"), dated September 25, 1997 (the "Agreement") and
the Amendments of March 25th, 1998, May 25, 1998 and June 25, 1998 extending the
Maturity Date of all of the Notes to February 25, 1999, and to the Senior
Secured Promissory Notes (the "Notes") and Common Stock Warrants (the
"Warrants") issued under the Agreement.

      Whereas, Xenometrix has demonstrated the ability to generate non-exclusive
licenses as evidenced by Aurora Biosciences Corporation (April 17, 1998); CEREP,
S.A. (June 5, 1998); Phase-1 Molecular Toxicology (July 27, 1998); Affymetrix,
Inc. (September 30, 1998) and Gene Logic, Inc. (October 12, 1998); and

      Whereas,  Xenometrix  is engaged  in  licensing  discussions  with
several companies; and

      Whereas,  Xenometrix is engaged in discussions  with other parties
that may lead to the sale of the Company,

      Now therefore, the Parties agree to amend the Agreement, Notes and
Warrants, as follows:

      The Funds agree to extend the Maturity Date of all of the Notes issued
under the Agreement to February 25, 1999, in exchange for Xenometrix paying to
the Funds a total of 38.5% of all gross licensing revenues received during the
extension period. Xenometrix will make these payments within five working days
of the receipt of said revenues. All payments shall be applied first to accrued
interest due on the principal balance up to the date of payment, and then to a
reduction of the principal balance.

      Xenometrix agrees to make best efforts to pursue its licensing strategy
during this extension.

      Xenometrix agrees to reduce the exercise price of the 499,994 warrants
previously issued to the Funds under the Agreement to $0.125 per share.

      The Funds agrees to continue to charge an interest rate of 12% during the
extension period.

      The Company shall not use the name of the Funds or any officer, director,
employee, affiliate or shareholder thereof without the express written consent
of the Funds and such person.

      In the event of an acquisition of Xenometrix by a third party, the unpaid
principal together with any accrued interest on the Notes shall be immediately
due and payable at the closing of such acquisition. In addition, if the Company
is acquired at a price per share that is greater than the exercise price of the
Warrants, the Funds agree to surrender all outstanding Warrants at the closing
of such acquisition in exchange for either cash or registered and freely
tradable common stock of the acquiring company in an aggregate amount calculated
by subtracting the exercise price of the Warrants from price per share paid to
Xenometrix shareholders, and multiplying the difference by the number of
Warrants outstanding at the closing.

      All other terms and conditions of the Agreement as amended will continue
to be in full force during the extension period.


<PAGE>   2

      In witness whereof, the Parties hereto have caused this Amendment to be
executed by their respective duly authorized representative as of October 25,
1998.



XENOMETRIX, INC.                    THE ARIES FUND, A CAYMAN ISLAND TRUST
                                    By:  its Investment Manager, PARAMOUNT
By:  /s/   Stephen J. Sullivan      CAPITAL ASSET MANAGEMENT, INC.
     -------------------------
        Stephen J. Sullivan         By:  /s/  Lindsay A. Rosenwald, M.D.
        President & CEO             ------------------------------------
                                             President


                                    THE ARIES DOMESTIC FUND, L.P.
                                    By:  its General Partner, PARAMOUNT
                                    CAPITAL ASSET MANAGEMENT, INC.

                                    By:  /s/  Lindsay A. Rosenwald, M.D.
                                         -------------------------------
                                            President