Specific but noncompetitive inhibition by 2-alkylthio analogues of adenosine 5'-monophosphate and adenosine 5'-triphosphate of human platelet aggregation induced by adenosine 5'-diphosphate

Some 2-alkylthio derivatives of adenosine 5'-monophosphate (AMP), adenosine 5'-monophosphorothioate (AMPS) and adenosine 5'-triphosphate (ATP) were examined as inhibitors of human platelet aggregation. 2-Methylthio-AMP, 2-ethylthio-AMP, 2-(pentan-l-yl)thio-AMP, 2-ethylthio-AMPS, 2-methylthio-ATP and 2-ethylthio-ATP (100 microM) each inhibited aggregation induced by adenosine 5'-diphosphate (ADP) but not by 11 alpha, 9 alpha-epoxymethano prostaglandin H2, a stable endoperoxide analogue. Log dose-response curves to ADP in the absence and presence of each inhibitor were not parallel and the inhibition could not be overcome by high concentrations of ADP. The ATP analogues achieved greater inhibition of aggregation induced by ADP (5 microM) than did the AMP analogues. The order of potency of the AMP analogues was 2-ethylthio-AMPS greater than 2-ethylthio-AMP greater than 2-(pentan-l-yl)thio-AMP greater than 2-methylthio-AMP, and 2-methylthio-ATP was more potent than 2-ethylthio-ATP. These 2-alkylthio substituted analogues of AMP and ATP are specific but noncompetitive inhibitors of ADP-induced human platelet aggregation.