EFFECTS OF N-ETHOXYCARBONYL-2-ETHOXY- 1,2-DIHYDROQIJINOLINE (EEDQ) IN EXPERIMENTAL CHLOROFORMEPINEPHRINE AND DIGITALIS DYSRHYTHMIAS

¹ Departments of Pharmacology and Therapeutics and Pathology, McGill University, Montreal, Quebec, Canada

In view of the well known antiarrhythmic actions of quinidine, it was of interest to investigate the cardiovascular effects and antidysrhythmic activity of N-ethoxycarbonyl-2-ethyl-1,2-dihydroquinoline (EEDQ), which belongs to a new series of dihydroquinolines, exerting both alpha adrenergic receptor blocking action and central nervous system depression. It is confirmed that in cats under pentobarbital anesthesia with artificial respiration, EEDQ (0.5-50 mg/kg i.v.) produced increasing degrees of hypotension with sinus, tachycardia, but no detectable "quinidine-like" electrocardiogram changes. Alpha adrenergic receptor blockade occurred rapidly (in two to three minutes) after EEDQ (5 mg/kg i.v.) and was prolonged (three to four hours or longer); there was also no evidence of beta adrenergic receptor blockade, and marked tachycardia was observed after epinephrine, norepinephrine or isoproterenol (10-µg/kg doses). EEDQ pretreatment prevented the pressor response and ventricular dysrhythznias after chloroform-epinephrine but did not prevent the pressor effects or the ectopic rhythms after ouabain, proscillaridin or digitoxin; both EEDQ and phenoxybenzamine enhanced the onset of digitalis ventricular fibrillation. It is suggested that the antidysrhythmic action observed after chloroform-epinephrine might be due indirectly to the associated fall in blood pressure (epinephrine reversal), but the enhanced digitalis cardiotoxicity (after EEDQ or phenoxybenzamine) appears to involve both reflex increased cardiac sympathetic stimulation and possibly central sympathetic excitatory effects of the cardiac glycosides.