Cardiovascular profile of 2-(3,4-diethyoxy-beta-methoxyphenethyl) imino-1-methylpyrrolidine fumarate (McN-2840-46), a preferential atrial anti-arrhythmic agent.

Abstract

McN-2840-46, 2.5 mg/kg, i.v., protected against atrial tachyarrhythmias induced by three different methods in dogs and monkeys. The compound was inactive against ventricular arrhythmias produced by ouabain and by chloroform-epinephrine interaction at a four-fold higher dose. Significant reversal of ventricular arrhythmias produced by occlusion of the left anterior descending coronary artery in dogs was achieved by infusion of 8.8 +/- 2.4 mg/kg, i.v. of McN-2840-46. Myocardial electrogram studies confirm that the atrium is preferentially affected. McN-2840-46 does not possess beta 1- or beta 2-adrenergic blocking activity when evaluated on isolated rabbit atrial and guinea-pit tracheal chain preparations. McN-2840-46 is vagolytic but not anticholinergic. The vagolytic activity is attributed to its local anesthetic effect. Depression of myocardial function was observed in anesthetized dogs and in the heart-lung preparation. However, the isolated cat papillary muscle was stimulated by McN-2840-46 and doses considerably above the effective anti-arrhythmic dose did not significantly decrease cardiac output in the non-anesthetized dog. The results of these experiments suggest that McN-2840-46 is a potent "preferential" atrial anti-arrhythmic agent.