ANTITHROMBOTIC ACTION OF TA-993, A NEW 1,5-BENZOTHIAZEPINE DERIVATIVE, IN A CANINE MODEL OF FEMORAL ARTERIAL THROMBOSIS

TA-993 is a novel 1,5-benzothiazepine derivative of l-cis configuratio n, having a potent antiplatelet action and an increasing action on fem oral blood flow. We evaluated the antithrombotic effect of TA-993 in a canine model of femoral arterial thrombosis. Thrombus was induced by both application of direct anodal current to the femoral artery and pa rtial occlusion of the artery. The partial occlusion by placing an adj ustable occluder on the artery and the current application were carrie d out 40 and 60 min after the intraduodenal administration of drugs, r espectively. in control dogs, complete sustained occlusion of the femo ral artery due to thrombus occurred 55.4 +/- 9.2 min after the onset o f current application. TA-993 (3 and 10 mg/kg) dose-dependently prolon ged the time for occlusion. Aspirin (30 mg/kg) also prolonged it. TA-9 93, 10 mg/kg, significantly inhibited whole-blood aggregation 60 min a fter the administration with a weaker potency than that of aspirin (30 mg/kg), whereas 3 mg/kg of TA-993 did not. The inhibitory effect of T A-993 (10 mg/kg) on platelet aggregation was maintained for >7 h. More over, TA-993 (10 mg/kg) increased femoral blood flow in spite of the p artially occluded condition. These results indicate that TA-993 has an antithrombotic effect on femoral arterial thrombosis and suggest that an increasing action on femoral blood flow of TA-993 is more relevant than its antiplatelet action to the antithrombotic effect in this mod el.