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.
2nd Tokushima Institute of New Drug Research, Otsuka Pharmaceutical Co. Ltd., Japan.
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H
Fujiki
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T
Mori
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K
Yoshida
T
T
Imaizumi
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M
Tominaga
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