Effects of verapamil and nisoldipine on human platelets: in vivo and in vitro studies

Jones, C.R.; Pasanisi, F.; Elliott, H.L.; Reid, J.L.

British Journal of Clinical Pharmacology 20(3): 191-196

1985


ISSN/ISBN: 0306-5251
PMID: 2994701
DOI: 10.1111/j.1365-2125.1985.tb05060.x
Accession: 005333211

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Abstract
1 Inhibition of platelet aggregation was observed after 4 days of oral dosing with the calcium antagonists, verapamil (160 mg) or nisoldipine (20 mg) but not following acute dosing. These effects were observed at plasma concentrations that had no effect on platelet aggregation when investigated in vitro. 2 Verapamil added in vitro inhibited adrenaline-induced platelet aggregation at relatively low concentrations (IC50 16 .mu.M) but not inhibited aggregation to adenosine diphosphate at very high concentrations (IC50 700 .mu.M). 3 Nisoldipine, a dihydropyridine, added in vitro had no effect on platelet aggregation induced by adenosine diphosphate but inhibited by 67%, the secondary phase of platelet aggregation induced by adrenaline. 4 Verapamil but not nisoldipine displaced [3H]-yohimbine from the specific binding sites on human platelets, suggesting an interaction with .alpha.2-adrenoceptors. 5 Inhibition of adrenaline-induced aggregation by verapamil in vitro may be a result of antagonism of .alpha.2-adrenoceptors but long term treatment with both verapamil and nisoldipine also inhibits platelet aggregation mechanisms other than by .alpha.2-adrenoceptor blockade.

Effects of verapamil and nisoldipine on human platelets: in vivo and in vitro studies