Comparative studies on the positive inotropic effect of isoproterenol and bromobenzoyl-methyladamantylamine in guinea pig ventricular myocardium.
The effects of bromobenzoyl-methyladamantylamine (BMA) on the transmembrane potentials, contractile force, and 42K efflux were investigated and compared to that of isoproterenol (IPR) in guinea pig ventricular myocardium. Both drugs exerted positive inotropic effect. BMA lengthened the action potential duration, depolarized the membrane, and decreased the Vmax. IPR increased the height of the plateau, accelerated repolarization, slightly increased the resting potential. In preparations depolarized partially by 26 mmol/l K+, both BMA (10(-4) mol/l) and IPR (10(-7) mol/l) induced slow response action potentials, but the duration of BMA-induced ones was twice longer than that of IPR-induced ones. BMA markedly reduced the 42K efflux from ventricular myocardium, whereas IPR had no effect on it. Moreover, BMA also decreased the 26 mmol/l K+-induced increment in 42K efflux, while IPR did not. It is concluded that BMA and IPR exert their positive inotropic effects on different ways. IPR increases the slow inward Ca2+ current directly by activating a phosphorylation process, whereas BMA enhances it indirectly by reducing the K+ conductance, lengthening the repolarization and consequently prolonging the time during which the slow inward Ca2+ current can be operative.
D000200:Action Potentials / Q000187:drug effects; D000547:Amantadine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013268:Stimulation, Chemical
D002316:Cardiotonic Agents; D007473:Ion Channels; C036548:4-bromobenzoyl-methyladamantylamine; D012964:Sodium; D000547:Amantadine; D007545:Isoproterenol; D011188:Potassium; D002118:Calcium