Study of antiarrhythmic activity 2-(n-butylpyrrolidine)-N-(2-bromophenyl)carboxamide hydrochloride

I. P. Rudakova, S. V. Chashchina, A. Starkova
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Abstract

Objective. To study the efficacy of a new derivative 2-(alkylpyrrolidine)-N-(aryl)carboxamide with high antiarrhythmic activity. Materials and methods. To study the antiarrhythmic activity of the compound, the experiment was carried out on models of arrhythmia caused by intravenous administration of aconitine and adrenaline. The effect was estimated by its ability to prevent the onset of arrhythmia, prolong the survival time of the animals or by the duration of an arrhythmia attack. In addition, the electrocardiogram of awake rats was analyzed. The studied compound and the comparison drug (lidocaine) were injected to the animals intravenously in effective antiarrhythmic doses. Results. In aconitine arrhythmia 2-(n-butylpyrrolidine)-N-(2-bromophenyl) carboxamide hydrochloride provides statistically significant limitation of the duration of arrhythmia attacks in experimental animals (1.7 times) in comparison with the control and also reduction of arrhythmia duration in comparison with lidocaine (2.5 times); besides, this compound guarantees animals’ survival in 100 % of cases. When causing arrhythmia by adrenaline administration, the compound does not prevent the occurrence of cardiac rhythm disorder. The electrocardiogram readings of animals do not change significantly. Conclusions. 2-(n-butylpyrrolidine)-N-(2-bromophenyl) carboxamide hydrochloride (compound K-23) shows visible activity in models of arrhythmia caused by administration of aconitine and calcium chloride, which may indicate its ability to impede the sodium flow through the cell membrane by slowing depolarization of cardiomyocytes. Since the compound studied, demonstrates high antiarrhythmic activity without changing the ECG readings, the drug created on its basis may be effective.
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抗心律失常活性研究 2-(正丁基吡咯烷)-N-(2-溴苯基)甲酰胺盐酸盐
目的研究具有高度抗心律失常活性的新衍生物 2-(烷基吡咯烷)-N-(芳基)甲酰胺的功效。材料和方法。为研究该化合物的抗心律失常活性,在静脉注射乌头碱和肾上腺素引起的心律失常模型上进行了实验。根据其防止心律失常发生、延长动物存活时间或心律失常发作持续时间的能力来评估其效果。此外,还对清醒大鼠的心电图进行了分析。研究的化合物和对比药物(利多卡因)以有效的抗心律失常剂量静脉注射给动物。结果在阿卡尼汀心律失常中,2-(正丁基吡咯烷)-N-(2-溴苯基)羧酰胺盐酸盐能显著缩短实验动物心律失常发作的持续时间(与对照组相比缩短了 1.7 倍),与利多卡因相比缩短了心律失常持续时间(2.5 倍)。当使用肾上腺素导致心律失常时,该化合物不能阻止心律失常的发生。动物的心电图读数没有明显变化。结论2-(正丁基吡咯烷)-N-(2-溴苯基)甲酰胺盐酸盐(化合物 K-23)在服用乌头碱和氯化钙引起的心律失常模型中显示出明显的活性,这可能表明它能够通过减缓心肌细胞的去极化来阻碍钠流通过细胞膜。由于所研究的化合物在不改变心电图读数的情况下显示出很高的抗心律失常活性,因此以其为基础研制的药物可能是有效的。
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