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.
D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D003864:Depression, Chemical; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects; D012701:Serotonin / Q000097:blood; D012702:Serotonin Antagonists / Q000494:pharmacology; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors; D014700:Verapamil / Q000494:pharmacology*
D012702:Serotonin Antagonists; D012701:Serotonin; D013929:Thromboxane B2; D014700:Verapamil; D004837:Epinephrine