Mitsuhashi H, Hashimoto K
Department of Pharmacology, Yamanashi Medical College, Japan.
Jpn J Pharmacol. 1988 Apr;46(4):349-58. doi: 10.1254/jjp.46.349.
Antiarrhythmic effects of AHR 10718 were examined using two-stage coronary ligation, digitalis and adrenaline-induced canine ventricular arrhythmias and aconitine-induced canine atrial arrhythmia. The minimum effective plasma concentration for each arrhythmia model was determined for quantitative analysis of the antiarrhythmic effects. AHR 10718 suppressed the above arrhythmias except for adrenaline-induced arrhythmia. The minimum effective plasma concentrations for arrhythmias induced by 24 hr coronary ligation, 48 hr coronary ligation and digitalis were 8.1 +/- 0.7 (by 10 mg/kg, i.v.), 2.9 +/- 0.9 (by 5 mg/kg, i.v.) and 2.8 +/- 0.6 (by 5 mg/kg, i.v.) microgram/ml, respectively (mean +/- S.D., n = 6). The correlation coefficients between the antiarrhythmic effects of AHR 10718 and its plasma concentrations were not high. This pharmacological profile is characteristic of class 1 Na channel blockers, and in particular, it is similar to those of disopyramide, procainamide and SUN 1165 from our previous studies. AHR 10718 is expected to become a clinically useful antiarrhythmic drug.
采用两阶段冠状动脉结扎、洋地黄和肾上腺素诱发的犬室性心律失常以及乌头碱诱发的犬房性心律失常模型，研究了AHR 10718的抗心律失常作用。测定了每种心律失常模型的最低有效血浆浓度，用于抗心律失常作用的定量分析。AHR 10718可抑制上述心律失常，但肾上腺素诱发的心律失常除外。24小时冠状动脉结扎、48小时冠状动脉结扎和洋地黄诱发的心律失常的最低有效血浆浓度分别为8.1±0.7（静脉注射10mg/kg）、2.9±0.9（静脉注射5mg/kg）和2.8±0.6（静脉注射5mg/kg）微克/毫升（平均值±标准差，n = 6）。AHR 10718的抗心律失常作用与其血浆浓度之间的相关系数不高。这种药理学特征是I类钠通道阻滞剂的特点，特别是与我们之前研究中的丙吡胺、普鲁卡因胺和SUN 1165相似。AHR 10718有望成为一种临床上有用的抗心律失常药物。
