CARDIAC EFFECTS OF KETANSERIN, A SEROTONIN ANTAGONIST : ELECTROPHYSIOLOGICAL EXAMINATIONS AS A PART OF TOXICITY STUDIES

Abstract

Cardiac effects of ketanserin were examined mainly electrophysiologically with using rat and guinea pig heart muscle preparations. 10^&lt-6&gtM ketanserin slightly antagonized the positive chronotropic but not inotropic action of serotonin in spontaneously beating guinea pig atria. Ketanserin, only at the concentration as high as 10^&lt-4&gtM, produced sIight rightward shift of the positive chronotropic but not inotropic dose-response curves for norepinephrine in guinea pig atria. In both rat and quinea pig atria, ketanserin per se produced negative chronotropic effect and slight prolongation of action potential duration (APD) at high concentrations, 0.1 or 0.3mg/ml. In guinea pig ventricular preparation, 1mg/ml of ketanserin did not affect the rate of rise of the action potential (+Vmax), action potential amplitude and APD. In rat ventritular free wall preparations, 1mg/ml of katanserin produced slight increase in APD without affecting the other action potential parameters. In rat ventricular papillary muscle and septum preparations, 0.3 mg/ml of katanserin tended to produce a decrease in +Vmax and an increase in APD. However, since these changes were produced only at extremely high concentrations and slight in degree, it was concluded that ketanserin does not produce electrophysiological side effects of clinical relevance.