Antidysrhythmic and electrophysiological effects of a new antianginal agent, bepridil.
Antidysrhythmic and electrophysiological effects of a new antianginal agent, bepridil.
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新型抗心绞痛药贝普地尔的抗心律失常和电生理作用。
DOI：
10.1097/00005344-198003000-00010
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发表时间：
1980
影响因子：
3
通讯作者：
E. Winslow
中科院分区：
文献类型：
--
作者：
K. Kane;E. Winslow
将新型抗心绞痛药贝普地尔的抗心律失常作用与已知的抗心律失常药物丙吡胺的抗心律失常作用进行了比较。苯普地尔（20、50 和 100 mg/kg，腹膜内注射）对小鼠乌头碱诱导的心律失常几乎没有保护作用，而类似剂量的丙吡胺却发挥了显着的剂量依赖性抗心律失常作用。静脉注射贝普地尔（2 mg/kg）或丙吡胺（10 mg/kg）可显着减少大鼠冠状动脉结扎后心室期外收缩的次数，并完全消除心室颤动的发生。还研究了贝普地尔的体外局部麻醉和电生理作用。在 0.01-0.05 mM 的浓度下，观察到脱鞘青蛙坐骨神经的动作电位高度显着但缓慢地降低。在绵羊浦肯野纤维中，使用贝普地尔（0.5-2 X 10(-5) M）观察到动作电位高度的类似降低，与动作电位零相去极化最大速率（MRD）的显着降低相关。需要更高的浓度(2-8 X 10(-5) M)来降低豚鼠心室肌的MRD。贝普地尔的抗心律失常作用至少可以部分地通过观察到的电生理学效应来解释。
The antidysrhythmic effects of a new antianginal agent, bepridil, were compared with those of disopyramide, a known antidysrhythmic drug. Bepridil (20, 50, and 100 mg/kg, i.p.) conferred little protection against aconitine-induced dysrhythmias in mice, whereas similar doses of disopyramide exerted a marked dose-dependent antidysrhythmic effect. Intravenous administration of either bepridil (2 mg/kg) or disopyramide (10 mg/kg) significantly reduced the number of ventricular extrasystoles and completely abolished the occurrence of ventricular fibrillation following coronary artery ligation in the rat. Local anesthetic and electrophysiological effects in vitro of bepridil were also investigated. A marked but slowly developing reduction in action potential height of desheathed frog sciatic nerves was observed at concentrations of 0.01-0.05 mM. In sheep Purkinje fibres, a similar decrease in action potential height, associated with a pronounced reduction in the maximum rate of depolarization of phase zero of the action potential (MRD) was seen with bepridil (0.5-2 X 10(-5) M). Higher concentrations (2-8 X 10(-5) M) were required to reduce MRD of guinea pig ventricular muscle. The antidysrhythmic actions of bepridil may at least in part be explained by the electrophysiological effects observed.