Ninomiya M, Toyama J, Kodama I, Yamada K
J Cardiovasc Pharmacol. 1984 Nov-Dec;6(6):1222-9.
The effects of 711389-S, a newly developed antiarrhythmic agent, on transmembrane action potentials were examined in isolated papillary muscles of guinea pigs. 711389-S above 10(-6) M caused a dose-dependent decrease in the maximum upstroke velocity (Vmax) and a slight prolongation of the action potential duration (APD) at a late repolarization phase. The resting potential, the amplitude, and APD at an early repolarization phase were not affected even at 10(-5) M. In the presence of 711389-S, trains of stimuli higher than 0.1 Hz led to an exponential decline in Vmax to a new plateau level. This use-dependent block was augmented at the higher stimulation frequency. The time constant for the recovery from the use-dependent block was 47 s at 3 X 10(-6) M. At 1.0 Hz, 711389-S caused an appreciable shift (6.8 mV) of the curve relating the membrane potential and Vmax along the voltage axis in the hyperpolarizing direction, but no shift at 0.1 Hz. The antagonistic effect of 711389-S against acetylcholine in guinea-pig isolated atria was much less than that of disopyramide. These findings suggest that 711389-S has similar electrophysiological effects to those of other Class Ia antiarrhythmic drugs but has much less anticholinergic activity.
在豚鼠离体乳头肌中研究了新开发的抗心律失常药物711389-S对跨膜动作电位的影响。浓度高于10(-6)M的711389-S可导致最大除极速度（Vmax）呈剂量依赖性降低，并使复极化后期的动作电位时程（APD）略有延长。即使在10(-5)M浓度下，静息电位、动作电位幅度及复极化早期的APD也不受影响。在存在711389-S的情况下，频率高于0.1Hz的刺激序列会导致Vmax呈指数下降至新的平台水平。这种频率依赖性阻滞在较高刺激频率时增强。在3×10(-6)M浓度下，从频率依赖性阻滞恢复的时间常数为47秒。在1.0Hz时，711389-S可使膜电位与Vmax关系曲线沿电压轴在超极化方向上有明显偏移（6.8mV），但在0.1Hz时无偏移。711389-S对豚鼠离体心房乙酰胆碱的拮抗作用远小于丙吡胺。这些发现表明，711389-S具有与其他Ia类抗心律失常药物相似的电生理作用，但抗胆碱能活性低得多。
