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 aggregati on in human platelets. All the basic metabolites (IC50:8-22 mu g/ml) h ad 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 al though nicardipine and nimodipine were less active than the other drug s. The inhibitory effect of clentiazem was enhanced in the presence of aspirin or ticlopidine. Diltiazem and nicardipine also exhibited a si milar potentiaton of the anti-platelet effect in combination with aspi rin or ticlopidine. Clentiazem also inhibited collagen-induced thrombo xaneB(2) production by the platelets, and this inhibition by clentiaze m was additively enhanced by the presence of aspirin. When both clenti azem and aspirin were orally administered to rats, platelet aggregatio n was additively inhibited. These results indicate that a combination therapy with clentiazem plus aspirin or clentiazem plus ticlopidine ma y be useful for the prevention and/or treatment of thrombotic disorder s.