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

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 microM. Inhibition of the Ca2+ current by cibenzoline (2 microM) was dependent upon stimulation frequency, with a greater block occurring at 2 Hz (approximately 50%) than at 0.2 Hz (approximately 15%). The magnitude of Ca2+ current block was also potential-dependent. A markedly greater inhibition by cibenzoline (20 microM) 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 microM) and a reduction in contractile force of isolated, electrically-stimulated papillary muscles of the guinea-pig (IC50 = 35 microM). Thus, cibenzoline possesses Ca2+ channel blocking (class 4) properties in addition to its local anaesthetic actions.