Cardiovascular effects of RS-5773, a novel benzothiazepine calcium-antagonist, in dogs

• Published in: Japanese Journal of Pharmacology 1992, Vol.58 (suppl.2), p.400-400
• Main Authors: Miyake, Shigeki, Shiga, Hiroshi, Mizuno, Hiroshi, Ito, Yuko, Yorikane, Ryousuke, Yanagisawa, Hiroaki, Fujimoto, Koichi, Koike, Hiroyuki
• Format: Article
• Language: English
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)49694-7

RS-5773 , (2S,3S)-3-acetoxy-8-benzyl-2,3- dihydro-5-「2-(dimethylamino)-ethyl」-2-(4-methoxyphenyl)-1,5-benzothiazepin-4-(5H)-one hydrochloride, is a newly synthesized Ca^2+ antagonist. RS-5773 (0.01 - 0.1 mg/kg, i.v.) produced dose dependent and long-lasting decreases in blood pressure (BP), total peripheral resistance (TPR) and heart rate (HR), and a slight increase in cardiac output in anesthetized dogs whose buffer nerves were severed. These actions of RS-5773 were more potent and long-lasting than those of diltiazem. In open chest dogs, the agent (0.05 - 0.2mg/kg, i.v.) decreased BP, HR and myocardial oxygen consumption (MVO_2 ), and increased coronary blood flow. The vasodilator action and MVO_2 decreasing action of RS-5773 were about 2 and 8 times more potent, respectively, than those of diltiazem. In conscious dogs, RS-5773 (1, 3 mg/kg, p.o.) produced a dose-related decrease in BP which lasted for more than 8 hr. These observations suggest that RS-5773 is useful in the treatment of ischemic heart diseases and hypertension.