Effect of NKH477, a novel cardiotonic agent, on the cardiovascular system in anesthetized dogs

• Published in: Japanese Journal of Pharmacology Vol. 52; no. suppl-1.1; p. 314
• Main Authors: Takahira, Takashi, Fujihara, Ryo, Hosono, Makoto, Nakamura, Keita
• Format: Journal Article
• Language: English
• Published: The Japanese Pharmacological Society 1990
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)55766-3

NKH477, 6-(3-dimethylaminopropionyl)forskolin, is a novel water-soluble forskolin derivative. We examined the cardiovascular effects of NKH477 in anesthetized dogs. Intravenous injections of NKH477(1～30μg/kg) caused dose-related increases in left ventricular dP/dtmax(LVdP/dtmax), coronary(CBF) and femoral blood flow, heart rate(HR) , and myocardial oxygen consumption(MVO_2 ) and a dose-related decrease in blood pressure(BP). The regression analysis between CBF and MVO_2 showed that NKH477 did not influence substantially the balance of oxygen supply and demand. Furthermore, intravenous infusions of NKH477(0.15～0.6μg/kg/min) increased LVdP/dtmax, cardiac output and HR, and decreased BP, pulmonary arterial diastolic pressure and total peripheral resistance in a dose-dependent manner. No arrhythmias were induced by NKH477 in all studies. These results suggest that NKH477 is effective in the treatment of congestive heart failure.