Inhibitory effect of clentiazem (TA-3090) on platelet aggregation--alone and in combination with aspirin or ticlopidine.

Clentiazem (a novel calcium antagonist) and its basic metabolites (MB1-MB7) showed inhibitory effects on collagen-induced platelet aggregation in human platelets. All the basic metabolites (IC50:8-22 mu g/ml) had much stronger inhibitory effects than clentiazem itself (IC50:53 mu g/ml), but the acidic metabolites (MA1-MA4) had no inhibitory effects even at 300 mu g/ml. Other calcium antagonists (diltiazem, verapamil, nicardipine and nimodipine) also showed similar inhibitory effects although nicardipine and nimodipine were less active than the other drugs. The inhibitory effect of clentiazem was enhanced in the presence of aspirin or ticlopidine. Diltiazem and nicardipine also exhibited a similar potentiaton of the anti-platelet effect in combination with aspirin or ticlopidine. Clentiazem also inhibited collagen-induced thromboxaneB(2) production by the platelets, and this inhibition by clentiazem was additively enhanced by the presence of aspirin. When both clentiazem and aspirin were orally administered to rats, platelet aggregation was additively inhibited. These results indicate that a combination therapy with clentiazem plus aspirin or clentiazem plus ticlopidine may be useful for the prevention and/or treatment of thrombotic disorders.