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Journal of Pharmacology And Experimental Therapeutics, Vol. 173, Issue 2, 323-335, 1970
Copyright © 1970 by American Society for Pharmacology and Experimental Therapeutics

THE ANTIARRHYTHMIC ACTIONS OF CARBAMAZEPINE (TEGRETOL)

CHARLES STEINER 1, ANDREW L. WIT 1, MELVIN B. WEISS 1, and ANTHONY N. DAMATO 1

1 Cardiopulmonary Laboratory, U.S. Public Health Service Hospital, Staten Island, New York

The antiarrhythmic actions of carbamazepine (C, Tegretol) were studied in vivo and in vitro. In 11 dogs with ventricular arrhythmias produced by digitalis, C (5 mg/kg i.v. or 30 mg/kg p.o.) restored sinus rhythm. Similarly, ventricular tachycardia, produced by coronary artery ligation, was converted to normal sinus rhythm by C (5 mg/kg i.v.) in four out of five dogs. The effect of C on interatrial, atrioventricular and intraventricular conduction was studied in 10 dogs, using multiple bipolar electrodes. Interatrial and intraventricular conduction was not affected by the drug; atrioventricular conduction was prolonged slightly. In four dogs with experimentally produced complete heart block, C (5 mg/kg i.v.) slowed the mean idioventricular rate from 48 to 36 beats/min without changing the sinus rate. C was studied in concentrations from 10-6 to 10-4 M in isolated perfused Purkinje fibers by the microelectrode technique. At 3 x 10-6 and 3 x 10-5 M, the action potential duration was shortened because of a decrease in the duration of the plateau (phase 2). The effective refractory period was also shortened by a smaller amount. C, in these doses, did not affect the amplitude or rate of rise (dv/dt) of phase O. In automatic fibers, C decreased the slope of phase 4 depolarization. Larger doses of C (10-4 M) caused further shortening of the action potential duration with a loss of resting potential and a decrease in the overshoot and dv/dt of phase 0.

Submitted on November 13, 1969
Accepted on February 27, 1970




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Copyright © 1970 by the American Society for Pharmacology and Experimental Therapeutics.