Positive inotropic effect of 3, 4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-qu inolinone (OPC-8212) in the dog with experimentally-induced right-sided heart failure.
The efficacy of orally active 3, 4-dihydro-6-[4-(3,4- dimethoxybenzoyl )-1-piperazinyl]-2(1H)- quin olinone ( OPC -8212) as a positive inotropic agent was examined using model right-sided heart failure dogs and compared with those of dobutamine and amrinone. Heart failure was produced in beagle dogs by a combination of tricuspid insufficiency and pulmonary stenosis, and then drugs were administered intravenously or orally. Intravenous OPC -8212, 1 and 3 mg/kg, amrinone, 1 and 3 mg/kg, and dobutamine, 0.01 and 0.03 mg/kg, increased the dP/dt of the right ventricular pressure for 5 to 10 min. These positive inotropic effects were accompanied by simultaneous increase in the heart rate in the cases of amrinone and dobutamine, and was accompanied by hypotension in the case of amrinone. However, OPC -8212 did not show such effects. This indicates that OPC -8212 has a relatively selective positive effect on cardiac contractility. Oral administration of OPC -8212, 10 to 100 mg/kg, and amrinone, 10 and 30 mg/kg, also showed a positive inotropic effect, appearing 1 h after administration and lasting up to the 5th h. Amrinone had about a 3 times stronger effect, but for similar positive inotropic effects, only amrinone showed positive chronotropic effect. The hypotensive effect of amrinone was also observed after oral administration, while such an effect was scarcely observed when using OPC -8212.
D000284:Administration, Oral; D000631:Aminopyridines / Q000494:pharmacology; D000676:Amrinone; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004280:Dobutamine / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006333:Heart Failure / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D011719:Pyrazines; D011804:Quinolines / Q000494:pharmacology*
D000631:Aminopyridines; D002316:Cardiotonic Agents; D011719:Pyrazines; D011804:Quinolines; D004280:Dobutamine; C041667:vesnarinone; D000676:Amrinone