Fujiki H, Mori T, Yoshida K, Imaizumi T, Tominaga M
2nd Tokushima Institute of New Drug Research, Otsuka Pharmaceutical Co. Ltd., Japan.
Eur J Pharmacol. 1996 Oct 17;313(3):191-200. doi: 10.1016/0014-2999(96)00507-9.
OPC-18790, (+/-)6-[3-(3,4-dimethoxybenzylamino)-2- hydroxypropoxy]-2(1H)-quinolinone, is a novel positive inotropic agent with a moderate vasodilating action. We examined the vasodilating action of OPC-18790 in detail in the pentobarbital-anesthetized dogs using a colored microsphere technique for resistance vessels and a mean circulatory filling pressure method for capacitance vessels. Intravenously (i.v.) infused OPC-18790 increased the first derivative of left ventricular pressure (LVdP/dt max), cardiac output, heart rate and decreased total peripheral resistance but did not affect mean blood pressure. OPC-18790 significantly increased arterial blood flow distribution to heart and decreased vascular resistance in heart. OPC-18790 at 300 micrograms/kg i.v. and nitroglycerin at 50 micrograms/kg i.v. did not affect mean circulatory filling pressure in intact anesthetized dogs, but both compounds decreased mean circulatory filling pressure in spinally anesthetized dogs. OPC-18790 also decreased resistance to venous return but nitroglycerin did not. These results suggest that OPC-18790 has both arterial and venous vasodilating actions in addition to its positive inotropic action. These actions may produce an improvement of cardiohemodynamics in heart failure.
OPC - 18790，即(±)6 - [3 - (3,4 - 二甲氧基苄基氨基)-2 - 羟基丙氧基]-2(1H)-喹啉酮，是一种新型的具有中等血管舒张作用的正性肌力药物。我们采用彩色微球技术研究阻力血管以及平均循环充盈压方法研究容量血管，在戊巴比妥麻醉的犬中详细检测了OPC - 18790的血管舒张作用。静脉注射OPC - 18790可增加左心室压力的一阶导数（LVdP/dt max）、心输出量、心率，并降低总外周阻力，但不影响平均血压。OPC - 18790显著增加心脏的动脉血流分布并降低心脏血管阻力。静脉注射300微克/千克的OPC - 18790和静脉注射50微克/千克的硝酸甘油对完整麻醉犬的平均循环充盈压无影响，但两种化合物均可降低脊髓麻醉犬的平均循环充盈压。OPC - 18790还降低了静脉回流阻力，而硝酸甘油则没有。这些结果表明，OPC - 18790除了具有正性肌力作用外，还具有动脉和静脉血管舒张作用。这些作用可能会改善心力衰竭患者的心脏血流动力学。
