EFFECTS ON RABBIT NODAL, ATRIAL, VENTRICULAR AND PURKINJE CELL POTENTIALS OF A NEW ANTIARRHYTHMIC DRUG, CIBENZOLINE, WHICH PROTECTS AGAINST ACTION POTENTIAL SHORTENING IN HYPOXIA

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Abstract
1 The effects of cibenzoline (UP 339–01), a new anti-arrhythmic drug, have been investigated in various cardiac tissues. 2 UP 339–01 produced a bradycardia, due partly to prolongation of the intracellularly recorded sinus node action potential duration (APD) and partly to depression of the maximum rate of depolarization (MRD). The slope of the slow diastolic depolarization was not significantly reduced. 3 UP 339–01 was not a β-adrenoceptor antagonist. 4 UP 339–01 was negatively inotropic, and shifted the relation between [Ca2+]o and force of contractions to the right, and increased A-H conduction time. It was concluded that UP 339–01 restricted slow inward current. 5 In all cardiac tissues depolarized by fast inward current, UP 339–01 caused a reduction in MRD and conduction velocity. The reduction was similar in atrial muscle, His and terminal Purkinje fibres, but in papillary muscle the effect was about half as great. On desheathed frog nerve UP 339–01 had a local anaesthetic potency slightly greater than that of procaine. 6 APD was significantly prolonged in a dose-related manner in ventricular muscle but to a lesser extent in the bundle of His and atrial tissue. In terminal Purkinje fibres APD50 and APD90 were unaltered, but the transient outward current (‘notch’) was abolished, resulting in a lengthening of APD20. 7 The effective and functional refractory periods of the A—V node and right bundle branch were both lengthened by UP 339–01 in a dose-related manner, and the difference between them was greatly increased. 8 UP 339–01 (2.63 μm) completely prevented the shortening of APD90 induced by hypoxia, and the shortening of APD50 and APD20 was much attenuated. There was no protection against hypoxic depression of contractions. 9 It was concluded that UP 339–01 is a highly active class 1 anti-arrhythmic agent with additional class 3 and 4 properties.

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