Komori S, Ishii M, Hashimoto K
Jpn J Pharmacol. 1985 May;38(1):73-82. doi: 10.1254/jjp.38.73.
Antiarrhythmic effects of intravenous coronary vasodilators (verapamil, diltiazem, bepridil, trimetazidine and nicorandil) were evaluated using two canine ventricular arrhythmia models (halothane-adrenaline arrhythmia and digitalis arrhythmia), and the minimum effective plasma concentrations of the drugs were determined for each arrhythmia model. Verapamil (0.1 mg/kg), diltiazem (0.1 mg/kg), bepridil (1 mg/kg) and high dose trimetazidine (10 mg/kg) were effective on halothane-adrenaline arrhythmia; and the minimum effective plasma concentrations of the above drugs were less than 30 +/- 10 ng/ml, less than 18 +/- 5 ng/ml, 0.38 +/- 0.11 microgram/ml and 7.0 +/- 1.5 micrograms/ml, respectively. Nicorandil (1 mg/kg) did not suppress halothane-adrenaline arrhythmia. Verapamil, diltiazem and bepridil must have suppressed the halothane-adrenaline arrhythmia by blocking the Ca channel. Verapamil (1 mg/kg), diltiazem (1 mg/kg), bepridil (5 mg/kg), trimetazidine (3 mg/kg) and nicorandil (3 mg/kg) were ineffective on digitalis arrhythmia, even though their maximum hypotensive doses were used.
使用两种犬室性心律失常模型（氟烷 - 肾上腺素性心律失常和洋地黄性心律失常）评估静脉注射冠状动脉血管扩张剂（维拉帕米、地尔硫䓬、苄普地尔、曲美他嗪和尼可地尔）的抗心律失常作用，并确定每种心律失常模型中药物的最低有效血浆浓度。维拉帕米（0.1mg/kg）、地尔硫䓬（0.1mg/kg）、苄普地尔（1mg/kg）和高剂量曲美他嗪（10mg/kg）对氟烷 - 肾上腺素性心律失常有效；上述药物的最低有效血浆浓度分别低于30±10ng/ml、低于18±5ng/ml、0.38±0.11μg/ml和7.0±1.5μg/ml。尼可地尔（1mg/kg）不能抑制氟烷 - 肾上腺素性心律失常。维拉帕米、地尔硫䓬和苄普地尔一定是通过阻断钙通道来抑制氟烷 - 肾上腺素性心律失常的。维拉帕米（1mg/kg）、地尔硫䓬（1mg/kg）、苄普地尔（5mg/kg）、曲美他嗪（3mg/kg）和尼可地尔（3mg/kg）即使使用最大降压剂量，对洋地黄性心律失常也无效。
