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Inhibition of the myocardial Ca 2+ inward current by the class 1 antiarrhythmic agent, cibenzoline
Author(s) -
Hoick Mark,
Osterrieder Wolfgang
Publication year - 1986
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1986.tb14588.x
Subject(s) - chemistry , electrophysiology , antiarrhythmic agent , patch clamp , medicine , ic50 , anti arrhythmia agents , biophysics , endocrinology , pharmacology , biology , biochemistry , in vitro , heart disease , atrial fibrillation
1 Cibenzoline, a class 1 (local anaesthetic‐type) antiarrhythmic drug, was investigated for possible effects upon the myocardial Ca 2+ inward current. 2 In voltage‐clamp experiments with isolated cardiac myocytes of guinea‐pig, cibenzoline caused a concentration‐dependent inhibition of the Ca 2+ current, with an IC 50 of 14 μ m . 3 Inhibition of the Ca 2+ current by cibenzoline (2 μ m ) was dependent upon stimulation frequency, with a greater block occurring at 2 Hz (∼ 50%) than at 0.2 Hz (∼ 15%). 4 The magnitude of Ca 2+ current block was also potential‐dependent. A markedly greater inhibition by cibenzoline (20 μ m ) 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. 5 Cibenzoline also caused a concentration‐dependent inhibition of KCl‐induced contractures of isolated aortic strips of the rat (IC 50 = 55 μ m ) and a reduction in contractile force of isolated, electrically‐stimulated papillary muscles of the guinea‐pig (IC 50 = 35 μ m ). 6 Thus, cibenzoline possesses Ca 2+ channel blocking (class 4) properties in addition to its local anaesthetic actions.