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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 J-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 J-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.