OPC-18790, a novel positive inotropic agent, has both arterial and venous vascular dilating actions in the dog.
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.
Fujiki
H
H
2nd Tokushima Institute of New Drug Research, Otsuka Pharmaceutical Co. Ltd., Japan.
Mori
T
T
Yoshida
K
K
Imaizumi
T
T
Tominaga
M
M
D000818:Animals; D017763:Autonomic Denervation; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008863:Microspheres; D015363:Quinolones / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D002316:Cardiotonic Agents; D015363:Quinolones; D014665:Vasodilator Agents; C077543:toborinone