Abstract
The effect of 2-methyl-3-(1, 4, 5, 6-tetrahydronicotinoyl) pyrazolo [1, 5-a] pyridine (KC-764) on human platelet aggregation and its mechanism of action were investigated. The inhibitory activity of KC-764 on arachidonic acid-induced platelet aggregation was most potent with IC50 of 4.2×10-8 M and was about 100 times more potent than that of acetylsalicylic acid (ASA). KC-764 weakly inhibited prostaglandin G2-and prostaglandin H2-induced platelet aggregations. Neither KC-764 nor ASA had effect on platelet aggregation induced with STA2 (thromboxane A2 analog). KC-764 inhibited strongly human platelet cyclooxygenase activity. The effect of KC-764 on platelet aggregation, differently from ASA, was reversible. The inhibitory effect of KC-764 on cyclic nucleotide phosphodiesterases was weak. KC-764 had no effect on the concentration of cAMP and cGMP.These results suggest that the reversible inhibitory effects of KC-764 on platelet aggregations are mediated mainly via inhibition of platelet cyclooxygenase.
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