Cardiovascular pharmacology of RS-1893, an orally active cardiotonic agent with arterial and venous vasodilator actions.

概要

論文の詳細を見る
RS-1893, 2-[2-chloro-4-(2, 3, 4, 5-tetrahydro-3-oxo-6-pyridazinyl)]-phenoxy-N-(2-morpholinoethyl)-acetamide, is a newly synthesized compound whose structure is different from that of cardiac glycosides and beta-stimulants. The in vitro cardiotonic action of RS-1893 was about 3 times more potent than that of milrinone. This action is most likely due to inhibition of phosphodiesterase-III, as has been suggested for many other cardiotonic agents . In pentobarbital anesthetized dogs, RS-1893 (1-30 μg/kg, i.v.) produced dose dependent increases in left ventricular dP/dt<SUB>max</SUB> and cardiac output and caused decreases in blood pressure and total peripheral resistance with a relatively small increase in heart rate. Central venous pressure decreased markedly, suggesting venous vasodilation. The in vivo cardiotonic action of RS-1893 was 3 times more potent than that of milrinone and was not affected in the presence of a large dose of propranolol. Oral administration of RS-1893 (0.03 and 0.1 mg/kg) also produced a dose-related increase in cardiac contractility in conscious beagles. The increase in LVdP/dt<SUB>max</SUB> reached a maximum in 1-3 hr after administration and lasted for more than 8 hr. Thus, RS-1893 appeared to be an orally active cardiotonic agent with vasodilator properties, probably acting on both arterioles and veins.
公益社団法人日本薬理学会の論文