Effects of verapamil and diltiazem on human platelet function.
In this study the antiplatelet properties of two calcium channel blockers, verapamil and diltiazem, were evaluated. In 20 random aspirin-abstaining donors, both diltiazem and verapamil (0.01-10 microM) reduced epinephrine-induced aggregation [46 +/- 6% (SE) inhibition] and demonstrated a dose-dependent inhibition of epinephrine-induced [14C]serotonin release (43 +/- 3% reduction). However, at equimolar concentrations, verapamil was twice as effective. Neither drug altered ADP, collagen, thrombin, or calcium ionophore-induced platelet aggregation or platelet granule secretion. Neither drug prevented formation of thromboxane B2 during secondary aggregation. Verapamil, but not diltiazem, increased the Kd of [3H]yohimbine binding from 2.03 to 46.99 nM without altering the calculated number of binding sites per platelet (124 sites/platelet). Supplemental calcium added to citrated platelet-rich plasma reversed both verapamil and diltiazem-induced inhibition of platelet aggregation. We conclude that, at the concentrations tested, both verapamil and diltiazem are specific inhibitors of epinephrine-induced platelet activation. Clearly, both agents may be acting by preventing epinephrine-induced increases in plasma membrane permeability to calcium. However, the greater potency of verapamil compared with diltiazem with only verapamil binding to alpha2-adrenergic receptors suggests that alpha-blockade represents a significant component of verapamil-induced platelet inhibition.
D001552:Benzazepines / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000378:metabolism; D004110:Diltiazem / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects; D010979:Platelet Function Tests; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D012701:Serotonin / Q000097:blood; D013929:Thromboxane B2 / Q000378:metabolism; D014700:Verapamil / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D001552:Benzazepines; D011942:Receptors, Adrenergic, alpha; D012701:Serotonin; D013929:Thromboxane B2; D014700:Verapamil; D004110:Diltiazem; D002118:Calcium; D004837:Epinephrine