5-AMINO-4-IMIDAZOLECARBOXAMIDE RIBOSIDE AND ITS NUCLEOBASE AS POTENTIATORS OF ANTIFOLATE TRANSPORT AND METABOLISM

摘要

The present invention provides a method for increasing the efficacy of antifolates which act via inhibition of dihydrofolate reductase (DHFR). The method comprises the steps of administration of 5-amino-4-imidazolecarboxarnide riboside (Z) or its base with the antifolate such that the targeted cells are exposed to both the antifolate and Z simultaneously. This results in increased influx of the antifolate. For MTX, accumulation of the more biologically active polyglutamate forms is also potentiated. This potentiation appears to be mediated by an effect on the RFC.