Effects of 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl] -2(1H)-quinolinone (OPC-8212), a new inotropic agent, on cardiotonic activity and coronary hemodynamics

Abstract

Cardiotonic activity and chronotropic effect of a new positive inotropic agent, 3,4-dihydro-6-[4-(3,4- dimethoxybenzoyl )-1-piperazinyl]-2(1H)- qu inolinone ( OPC -8212), were studied in isolated canine hearts eliminating the secondary effect due to neurohumoral alterations. Positive inotropic action of OPC -8212 was dose-dependent and its potency was equivalent to about 1/10(5) of isoprenaline (isoproterenol). However, the duration of action was two to three times longer than that of isoprenaline, and arrhythmogenic activity was not observed at any dose studied. An index of inotropic state, Emax, was increased by this agent even under the blockade of beta-adrenoceptors, indicating that the positive inotropic effect of this agent is not due to a stimulation of beta-adrenoceptors. the ventricular relaxation rate was enhanced dose-dependently in similar extent to the equivalent dose of isoprenaline. Effects of this agent on coronary blood flow (CBF) and myocardial oxygen consumption (MVO2) were also assessed in open chest dogs, eliminating secondary increases in these parameters due to an increase in mechanical load or heart rate. OPC -8212 increased MVO2 significantly even without significant alterations in heart rate and LV pressure. These increases both in CBF and MVO2 were similar to those of isoprenaline while arterio-venous difference in oxygen content was not affected by OPC -8212. Thus, we conclude that the efficiency of myocardial oxygenation of OPC -8212 is similar to that of isoprenaline and a direct coronary vasodilatory effect of this agent is minimal.