Nishimoto M, Hashimoto H, Ozaki T, Nagashima S, Nakashima M
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Naunyn Schmiedebergs Arch Pharmacol. 1990 Mar;341(3):240-5. doi: 10.1007/BF00169737.
The effects of mianserin, a tetracyclic antidepressant, and adinazolam, a new triazolobenzodiazepine which has antidepressant activity, on intraventricular conduction and the incidence of arrhythmias induced by programmed ventricular stimulation were studied in the dog heart after myocardial infarction and compared to the effects of amitriptyline, a standard tricyclic antidepressant. Amitriptyline at a dose of 1 mg/kg significantly slowed ventricular conduction in a frequency-dependent manner and at doses of 2 and 3 mg/kg significantly slowed ventricular conduction in infarcted ventricular myocardium. Amitriptyline also significantly slowed ventricular conduction in normal myocardium. Amitriptyline increased the incidence of ventricular arrhythmias induced by the programmed ventricular stimulation and prolonged the intraventricular delayed conduction resulting in re-entrant ventricular arrhythmia. On the other hand, mianserin and adinazolam at doses of 1-3 mg/kg had no significant effects on intraventricular conduction in infarcted and normal myocardium and on the incidence of arrhythmias induced by programmed ventricular stimulation. From these results, we can expect that mianserin and adinazolam may have a much lower cardiac toxicity than amitriptyline.
研究了四环类抗抑郁药米安色林和具有抗抑郁活性的新型三唑并苯二氮䓬类药物阿地唑仑对心肌梗死后犬心室内传导及程序性心室刺激诱发心律失常发生率的影响,并与标准三环类抗抑郁药阿米替林的作用进行了比较。剂量为1mg/kg的阿米替林以频率依赖性方式显著减慢心室传导,剂量为2mg/kg和3mg/kg时,可显著减慢梗死心室心肌的心室传导。阿米替林也显著减慢正常心肌的心室传导。阿米替林增加了程序性心室刺激诱发的室性心律失常的发生率,并延长了导致折返性室性心律失常的心室内延迟传导。另一方面,剂量为1 - 3mg/kg的米安色林和阿地唑仑对梗死和正常心肌的心室内传导以及程序性心室刺激诱发的心律失常发生率均无显著影响。从这些结果来看,我们可以预期米安色林和阿地唑仑的心脏毒性可能比阿米替林低得多。