Positive inotropic effect of 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1 -piperazinyl]-2(1H)-quinolinone (OPC-8212) and mechanism of action in guinea pig ventricular myocardium.

Effects of 3,4-dihydro-6-[4-(3,4- dimethoxybenzoyl )-1-piperazinyl]-2(1H)- qu inolinone ( OPC -8212) on the isolated guinea-pig ventricular myocardium was studied measuring the force of contraction and action potential under various experimental conditions. The positive inotropic effect (PIE) of OPC -8212 was observed at a concentration higher than 10(-5) mol/l. The following circumstantial evidence led to the conclusion that OPC -8212 caused an elevated cyclic AMP level in myocardial cells thereby producing the positive inotropic effect. The positive inotropic effect of OPC -8212 was unaffected by reserpinization, propranolol and cimetidine treatments. OPC -8212 strengthened the slow response of partially depolarized papillary muscle. This suggested an increased calcium influx across myocardial cell membrane. Carbachol inhibited the positive inotropic effect of OPC -8212 on ventricular myocardium. Concentration-effect curves for isoprenaline (isoproterenol) and histamine were shifted to the left but that for dihydro-ouabain was not affected at all by OPC -8212. Rested-state contraction of guinea-pig papillary muscle was strengthened by OPC -8212 the same as dibutyryl cyclic AMP and beta-agonists.