Inhibition of platelet aggregation by diltiazem. Comparison with verapamil and nifedipine and inhibitory potencies of diltiazem metabolites.
The inhibitory effects of three calcium blockers, diltiazem (d-form), verapamil, and nifedipine, on ADP- and collagen-induced platelet aggregation of human and rabbit platelets were compared. The potency of diltiazem was greater than those of verapamil and nifedipine in human platelet-rich plasma. A similar order of the inhibitory potencies was observed in rabbit platelet-rich plasma, but this order was reversed when washed platelets were aggregated in buffered saline. Antiaggregatory potencies of metabolites on diltiazem and their optical isomers were examined in human platelet-rich plasma. All the metabolites except deacetyl-N-demethyl diltiazem showed greater activity than diltiazem in ADP- or collagen-induced platelet aggregation. The potencies of the l-isomers of the deacetyl-N-demethyl metabolites were greater than those of the d-isomers. On the other hand, the inhibitory effect of the d-isomer of deacetyl-O-demethyl diltiazem was greater than that of the l-form at lower concentrations, whereas the relationship was opposite at higher concentrations. There was no marked difference in antiaggregatory potency between the d- and l-forms of diltiazem and N-demethyl diltiazem.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004110:Diltiazem / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D011817:Rabbits; D013237:Stereoisomerism; D014700:Verapamil / Q000494:pharmacology*
D001552:Benzazepines; D002121:Calcium Channel Blockers; D011725:Pyridines; D000244:Adenosine Diphosphate; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine