COMPARATIVE ACTIONS OF BETA-ADRENERGIC RECEPTOR BLOCKING DRUGS ON CONTRACTILE AND ELECTRICAL PROPERTIES OF ISOLATED HUMAN ATRIAL MUSCLE

Three β-adrenergic receptor Mocking drugs, propranolol, solalol (MJ-1999) and Kö-592 were studied for their effects on the contractile and electrical properties of isolated, human atrial muscle. Propranolol and solalol were found to be competitive antagonists of isoproterenol-induced changes in heart rate of spontaneously heating atrial preparations. Propranolol was approximately 10-15 times more potent than solalol in this antagonism. In concentrations several times that needed to produce marked β-adrenergic blockade, solalol produced only a transient negative inotropic effect on electrically driven atrial preparations. Propranolol, in the same relative beta-blocking concentration, produced a marked negative inotropic effect, culminating in the development of arrhythmias and ultimate asystole. Compound Kö-592, previously demonstrated to be equipotent with propranolol as a β-adrenergic antagonist in animal tissue, had a slight negative inotropic effect as did propranolol when tested in concentrations 2.5 times their isoproterenol blocking doses. Propranolol and solalol had minimal or no effects on the electrical excitability of the atrial preparations even when studied in concentrations many times greater than effective β-blocking doses. The data agree with other animal and human findings, suggesting thai solalol may have less propensity for producing a myocardial depressant effect on the human heart than does propranolol. © 1968 S. Karger AG, Basel.