Kaburaki M, Narita H, Yabana H, Karasawa T, Doi H, Murata S
Pharmaceutical Development Research Laboratory, Tanabe Seiyaku Co., Ltd., Toda, Saitama, Japan.
J Cardiovasc Pharmacol. 1998 Feb;31(2):240-7. doi: 10.1097/00005344-199802000-00009.
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 (> or = 10 microg/kg, i.v.) significantly increased blood flows of common carotid, brachial, and femoral arteries. The peak of its effect was observed approximately 60 min after the administration, and the peak level was maintained until > or = 300 min after the administration. TA-993 (100 microg/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 approximately 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.
TA - 993是一种具有l - 顺式构型的新型1,5 - 苯并硫氮杂卓衍生物，具有强大的抗血小板聚集作用。我们以地尔硫卓作为参比化合物，研究了其在麻醉犬体内的心血管效应。TA - 993（静脉注射，≥10微克/千克）显著增加了颈总动脉、肱动脉和股动脉的血流量。给药后约60分钟观察到其效应峰值，且峰值水平维持至给药后≥300分钟。TA - 993（静脉注射，100微克/千克）以相同方式轻微增加心输出量。然而，TA - 993对动脉血压、左心室dp/dtmax或椎动脉、冠状动脉、肠系膜上动脉和肾血流量没有产生任何持续性影响。TA - 993可使由40 mM钾离子收缩的离体犬股动脉产生浓度依赖性血管舒张，但其效力约为地尔硫卓的1/20。在麻醉犬中，六甲铵预处理可完全抑制TA - 993对股血流量的增加作用。这些结果表明，TA - 993对颈总动脉、肱动脉和股动脉血流量具有选择性增加作用，并提示该作用是由自主神经系统介导的。
