CARDIOVASCULAR EFFECT OF A NEW 1,5-BENZOTHIAZEPINE DERIVATIVE TA-993 IN ANESTHETIZED DOGS

TA-993 is a new 1,5-benzothiazepine derivative having l-cis configurat ion and shows a potent antiplatelet aggregating action. We studied its cardiovascular effect in anesthetized dogs by using diltiazem as a re ference compound. TA-993 (greater than or equal to 10 mu g/kg, i.v.) s ignificantly increased blood flows of common carotid, brachial, and fe moral arteries, The peak of its effect was observed similar to 60 min after the administration and the peak level was maintained until great er than or equal to 300 min after the administration. TA-993 (100 mu g /kg, i.v.) slightly increased cardiac output in the same manner. Howev er, TA-993 did not cause any persistent effects on arterial pressure, LVdP/dt(max), or vertebral, coronary, superior mesenteric, and renal b lood flows. TA-993 caused concentration-dependent vasorelaxation in th e isolated canine femoral artery contracted with 40 mM K+, but its pot ency was similar to 1/20 that of diltiazem. The increasing action of T A-993 on femoral blood flow was completely inhibited by pretreatment w ith hexamethonium in anesthetized dogs. These results indicate that TA -993 has a selective increasing action on common carotid, brachial, an d femoral blood flows and suggest that the action is mediated by the a utonomic nervous system.