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                                                                    Exhibit 4.2


                              AMENDMENT NUMBER ONE
                                     TO THE
                              AMENDED AND RESTATED
                          CERTIFICATE OF INCORPORATION
                      (FILED PURSUANT TO SECTION 242 OF THE
                        DELAWARE GENERAL CORPORATION LAW)
                                       OF
                              CV THERAPEUTICS, INC.



                  Louis G. Lange, M.D., Ph.D. does hereby certify that:

                  1.    He is the Chairman of the Board and Chief Executive
Officer of CV Therapeutics, Inc., a corporation organized and existing under
the laws of the state of Delaware. The original Certificate of Incorporation
was filed with the Secretary of State of the State of Delaware on December
11, 1990, and the Amended and Restated Certificate of Incorporation was filed
with the Secretary of State of the State of Delaware on November 22, 1996.

                  2.    The Amended and Restated Certificate of Incorporation
of this corporation is hereby amended as follows:

         Article IV, Section (A) is amended to read in full:

                        A.       The Corporation is authorized to issue two
         classes of stock to be designated, respectively, "Common Stock" and
         "Preferred Stock." The total number of shares which the corporation
         is authorized to issue is ninety million (90,000,000) shares.
         Eighty-five million (85,000,000) shares shall be Common Stock each
         having a par value of one tenth of one cent ($.001). Five million
         (5,000,000) shares shall be Preferred Stock, each having a par value
         of one tenth of one cent ($.001).

                                    * * * *

                  3.    The foregoing Amendment Number One to the Amended and
         Restated Certificate of Incorporation has been duly approved by the
         Board of Directors of this Corporation.

                  4.    The foregoing Amendment Number One to the Amended and
         Restated Certificate of Incorporation has been duly approved by the
         vote of the stockholders in accordance with Section 242 of the Delaware
         General Corporation Law. The total number of outstanding shares of the
         Corporation entitled to vote on the amendment was 19,437,644 shares of
         Common Stock as of November 10, 2000. The number of shares voting in
         favor of the amendment equaled or exceeded the vote required. The
         percentage vote required was more than 50% of the Common Stock.



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         IN WITNESS WHEREOF, CV Therapeutics, Inc. has caused this Amendment
Number One to the Amended and Restated Certificate of Incorporation to be signed
by the Chairman of the Board and Chief Executive Officer this 12th day of
December, 2000.



                                       CV THERAPEUTICS, INC.



                                       By:      /s/ Louis G. Lange
                                          -----------------------------------
                                                Louis G. Lange, M.D., Ph.D.
                                                Chairman of the Board and
                                                Chief Executive Officer



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