Inhibition of human platelet function by verapamil.

We evaluated the ability of the calcium antagonist, verapamil, to alter human platelet function. With the concentrations tested (20 ng to 0.1 mg/ml of whole blood), verapamil inhibited epinephrine-induced aggregation and release of 14C-serotonin; produced a dose-dependent inhibition of 14C-serotonin uptake and prevented aggregation dependent release of thromboxane B2. The action of verapamil could be overcome by higher concentrations of both epinephrine and calcium. Furthermore, verapamil-induced inhibition could be reversed by gel-filtering platelets suggesting that verapamil's anti-platelet activity does not outlast its presence in plasma. Verapamil was relatively ineffective as an inhibitor of ADP-induced aggregation. As with epinephrine-induced platelet activation, the effects of verapamil on ADP-induced 14C-serotonin and thromboxane release correlated with its effects on secondary aggregation. Finally, verapamil failed to alter calcium ionophore-induced platelet aggregation. Thus, verapamil at the concentrations tested, appears to be functioning as a reversible, relatively specific inhibitor of epinephrine-induced platelet activation. Our findings suggest that the actions of verapamil in this regard are complex; there may be competitive inhibition of epinephrine binding as well as a blockade of epinephrine-induced calcium flux.