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 configuration and shows a potent antiplatelet aggregating action. We studied its cardiovascular effect in anesthetized dogs by using diltiazem as a reference compound. TA-993 (≥10μg/kg, i.v.) significantly increased blood flows of common carotid, brachial, and femoral arteries. The peak of its effect was observed ∼60 min after the administration, and the peak level was maintained until ≥300 min after the administration. TA-993(100 μg/kg, i.v.) slightly increased cardiac output in the same manner. However, TA-993 did not cause any persistent effects on arterial pressure, LVdP/dtmax, or vertebral, coronary, superior mesenteric, and renal blood flows. TA-993 caused concentration-dependent vasorelaxation in the isolated canine femoral artery contracted with 40 mM K, but its potency was ∼1/20 that of diltiazem. The increasing action of TA-993 on femoral blood flow was completely inhibited by pretreatment with hexamethonium in anesthetized dogs. These results indicate that TA-993 has a selective increasing action on common carotid, brachial, and femoral blood flows and suggest that the action is mediated by the autonomic nervous system.