Satoh H, Ishii M, Hashimoto K
Department of Pharmacology, Yamanashi Medical College, Japan.
Jpn J Pharmacol. 1987 Jun;44(2):113-9. doi: 10.1254/jjp.44.113.
Effect of cibenzoline, a class I (local anesthetic-type) antiarrhythmic drug, was investigated upon canine ventricular muscle using a conventional micro-electrode method. In the presence of cibenzoline at the concentration of 3 X 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 Ia, 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 X 10(-6) M and 8 X 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.
使用传统微电极方法研究了I类（局部麻醉药型）抗心律失常药物西苯唑啉对犬心室肌的作用。当存在浓度为3×10⁻⁶ M或更高的西苯唑啉时，动作电位的最大上升速率受到抑制，动作电位持续时间以浓度依赖性方式显著延长。有效不应期也延长。根据 Vaughan Williams抗心律失常药物分类，从其对动作电位持续时间的影响来看，西苯唑啉应属于Ia类。另一方面，随着刺激频率增加（使用依赖性阻滞），西苯唑啉对最大去极化速率的抑制作用增强。在浓度为3×10⁻⁶ M和8×10⁻⁶ M的西苯唑啉存在下，在180次/分钟时最大去极化速率分别被阻滞36%和67%，最大去极化速率抑制的起始速率分别为0.109±0.027和0.146±0.070 AP⁻¹（平均值±标准差）。从最大去极化速率抑制的动力学来看，这些结果表明西苯唑啉应归类为一种可延长动作电位持续时间的中间型药物。
