Inhibition of the myocardial Ca2+ inward current by the class 1 antiarrhythmic agent, cibenzoline

Abstract

Cibenzoline, a class 1 (local anaesthetic‐type) antiarrhythmic drug, was investigated for possible effects upon the myocardial Ca2+ inward current. In voltage‐clamp experiments with isolated cardiac myocytes of guinea‐pig, cibenzoline caused a concentration‐dependent inhibition of the Ca2+ current, with an IC50 of 14 μm. Inhibition of the Ca2+ current by cibenzoline (2 μm) was dependent upon stimulation frequency, with a greater block occurring at 2 Hz (∼ 50%) than at 0.2 Hz (∼ 15%). The magnitude of Ca2+ current block was also potential‐dependent. A markedly greater inhibition by cibenzoline (20 μm) was recorded when myocytes were depolarized (to + 20 mV) from a holding potential of − 35 mV than of − 80 mV. At the less negative potential, cibenzoline also caused a reduction in the level of the holding current, which suggests a decrease in the inwardly rectifying K+ current. Cibenzoline also caused a concentration‐dependent inhibition of KCl‐induced contractures of isolated aortic strips of the rat (IC50 = 55 μm) and a reduction in contractile force of isolated, electrically‐stimulated papillary muscles of the guinea‐pig (IC50 = 35 μm). Thus, cibenzoline possesses Ca2+ channel blocking (class 4) properties in addition to its local anaesthetic actions. 1986 British Pharmacological Society