title: Differential inhibition of 2'-deoxycytidine salvage as a possible mechanism for potentiation of the anti-human immunodeficiency virus activity of 2',3'-dideoxycytidine by dipyridamole.
abstract: Dipyridamole, a commonly used coronary vasodilator and antithrombotic drug, was recently shown to potentiate the activity of 3'-azido-3'-deoxythymidine and 2',3'-dideoxycytidine against the human immunodeficiency virus type 1 (HIV-1) in human monocyte-macrophages in vitro. We report in the present paper that in uninfected monocyte-macrophages dipyridamole significantly inhibits cellular salvage of [3H]deoxycytidine, whereas it does not affect the salvage of [3H]dideoxycytidine. Similar differential inhibition by dipyridamole of the salvage of thymidine, as opposed to 3'-azido-3'-deoxythymidine, was reported previously (G. V. Betageri, J. Szebeni, K. Hung, S. S. Patel, L. M. Wahl, M. Corcoran, and J. N. Weinstein, Biochem. Pharmacol. 40:867-870, 1990). Taken together, these observations suggest that inhibition of the salvage of competing physiological nucleosides may explain or contribute to the potentiating effect of dipyridamole on these antiviral dideoxynucleoside drugs.
authors.affiliation: National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: S S
authors.initials: SS
authors.lastname: Patel
authors.forename: J
authors.initials: J
authors.lastname: Szebeni
authors.forename: L M
authors.initials: LM
authors.lastname: Wahl
authors.forename: J N
authors.initials: JN
authors.lastname: Weinstein
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003841:Deoxycytidine / Q000378:metabolism*; D004176:Dipyridamole / Q000494:pharmacology*; D004357:Drug Synergism; D015497:HIV-1 / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D009000:Monocytes / Q000382:microbiology; D010766:Phosphorylation; D016047:Zalcitabine / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D003841:Deoxycytidine; D004176:Dipyridamole; D016047:Zalcitabine