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.
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002927:Cimetidine / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology; D011719:Pyrazines; D011804:Quinolines / Q000494:pharmacology*; D012110:Reserpine / Q000494:pharmacology
D002316:Cardiotonic Agents; D011719:Pyrazines; D011804:Quinolines; C041667:vesnarinone; D002927:Cimetidine; D006632:Histamine; D012110:Reserpine; D002217:Carbachol; D011433:Propranolol; D000242:Cyclic AMP; D007545:Isoproterenol