Effect of Ca2+-antagonistic vasodilators, diltiazem, nifedipine, perhexiline and verapamil, on platelet aggregation in vitro.

Ca2+-Antagonistic vasodilators, diltiazem, nifedipine, perhexiline and verapamil, showed inhibitory activity on platelet aggregation in human platelet-rich plasma (PRP) induced with ADP, adrenaline and collagen. Preincubation of PRP with one of the drugs effectively prevented the aggregation induced by ADP, ID50s being 2.1 x 10(-4), 3.5 x 10(-5), 3.4 x 10(-5) and 2.3 x 10(-4) g/ml for diltiazem, nifedipine, perhexiline and verapamil, respectively. Nifedipine and perhexiline were equipotent and about 10 times as potent as diltiazem and verapamil. In addition, PRP maximally aggregated with 9.1 mumol/l ADP was disaggregated by administration of any of these drugs. The mechanism of action was considered to be Ca2+-antagonism because, with the exception of perhexiline, the potency ratio of the anti-aggregating activity had a close resemblance to that of the vasodilator activity of these drugs previously reported in the literature. Perhexiline showed the most potent anti-aggregating activity but has been reported to be the least potent vasodilator among the Ca2+-antagonists studied. This further studies are necessary to elucidate the mechanism of perhexiline's inhibition of platelet aggregation.