CARDIAC ACTIVITIES OF SEVERAL MONOAMINE OXIDASE INHIBITORS

¹ Departments of Pharmacology and Toxicology, The Yonsei University School of Medicine, Seoul, Korea, and The University of Wisconsin, Madison, Wisconsin

The effects of five monoamine oxidase (MAO) inhibitors (SKF-385, JB-516, W-1544, ephedrine and iproniazid) were examined on the isolated papillary muscle and auricles of the cat.

Iproniazid exerted only a negative inotropic effect on either papillary muscles or auricles. This action was blocked by neither atropine nor dichloroisoproterenol. Similar results were obtained with cardiac preparations from reserpine-treated cats.

SKF-385, JB-516 and W-1544 displayed cardiostimulant activities similar to those of ephedrine and the effects were blocked by dichloroisoproterenol. These MAO inhibitors failed to produce their stimulant effects on cardiac tissue which had been depleted of catecholamines by treatment of the animal with reserpine. However, prior exposure of the muscle to levarterenol or l-epinephrine restored the cardiostimulant capacity of the MAO inhibitors. On the basis of these findings it is concluded that the cardiostimulant effects of SKF-385, JB-516, W-1544 and ephedrine are mediated via a catecholamine-release mechanism.

SKF-385, JB-516, W-1544 and ephedrine failed to potentiate the effects of levarterenol or l-epinephrine on cardiac preparations from normal cats but markedly enhanced the effects of these amines on papillary muscles and auricles from reserpine-treated animals. To explain these results it was suggested that the MAO inhibitors may interfere with the binding of catecholamines to certain elements in the heart with the result that additional amounts of norepinephrine or epinephrine are made available to act on adrenergic receptors. The storage and release of myocardial catecholamines in relation to these elements in the heart were discussed.