Effect of Cibenzoline, a Class I Antiarrhythmic Drug, on Action Potential in Canine Ventricular Muscle

Abstract

Effect of cibenzoline, a class I (local anesthetic-type) antiarrhythmic drug, was investigated upon canine ventricular muscle using a conventional microelectrode method. In the presence of cibenzoline at the concentration of 3×10^-6 M or higher, the maximum rate of rise of the action potential was inhibited and the action potential duration was lengthened significantly in a concentration-dependent manner. The effective refractory period was also prolonged. From its effect on the action potential duration, cibenzoline should belong to la, according to the Vaughan Williams classification of antiarrhythmic agents. On the other hand, cibenzoline inhibition of the maximum rate of depolarization was greater with an increase in stimulation frequency (a use-dependent block). In the presence of cibenzoline concentrations of 3×10^-6 M and 8×10^-6 M, which blocked the maximum rate of depolarization by 36% and 67% at 180 beats/min, the rates of onset of inhibition of the maximum rate of depolarization were 0.109±0.027 and 0.146±0.070 AP^-1 (mean±S.D.), respectively. From the kinetics of inhibition of the maximum rate of depolarization, these results suggest that cibenzoline should be classified as an intermediate drug with the prolongation of the action potential duration.