Zhenjiu W, Awaji T, Hirasawa A, Motomura S, Hashimoto K
Department of Pharmacology, Yamanashi Medical College, Japan.
Mol Cell Biochem. 1993 Feb 17;119(1-2):159-69. doi: 10.1007/BF00926867.
The antiarrhythmic and direct cardiovascular effects of a new antiarrhythmic agent, bidisomide, alpha-(2-[acetyl(1-methylethyl)amino]ethyl)-alpha-(2- chlorophenyl)-1-piperidinebutanamide, were investigated. To determine the anti-arrhythmic effects, spontaneously occurring adrenaline-, digitalis- and two-stage coronary ligation-induced arrhythmias were used. Bidisomide suppressed these three arrhythmia models. The antiarrhythmic plasma concentration, IC50, of bidisomide for digitalis-induced arrhythmia was 22.1 micrograms/ml, and those calculated for intravenous bidisomide in 24 h and 48 h coronary ligation-arrhythmias were 15.1 and 11.6 micrograms/ml and that calculated for oral bidisomide in 24 h coronary ligation-arrhythmia was 5.4 micrograms/ml and that for adrenaline induced arrhythmia was 58.7 micrograms/ml. In the blood perfused sinoatrial node and papillary muscle preparations, bidisomide decreased the sinoatrial rate and contractile force and increased the intraventricular conduction time and coronary blood flow. These results indicate that bidisomide is similar to other class I antiarrhythmic agents such as pirmenol and KW-3401 in its antiarrhythmic profile and is expected to become a clinically useful antiarrhythmic drug.
研究了一种新型抗心律失常药物比地索胺（α-(2-[乙酰(1-甲基乙基)氨基]乙基)-α-(2-氯苯基)-1-哌啶丁酰胺）的抗心律失常作用及直接心血管效应。为确定其抗心律失常作用，采用了自发性肾上腺素、洋地黄及两阶段冠状动脉结扎诱导的心律失常模型。比地索胺可抑制这三种心律失常模型。比地索胺对洋地黄诱导的心律失常的抗心律失常血浆浓度IC50为22.1微克/毫升，静脉注射比地索胺对24小时和48小时冠状动脉结扎诱导的心律失常的计算值分别为15.1和11.6微克/毫升，口服比地索胺对24小时冠状动脉结扎诱导的心律失常的计算值为5.4微克/毫升，对肾上腺素诱导的心律失常的计算值为58.7微克/毫升。在血液灌流的窦房结和乳头肌标本中，比地索胺可降低窦房结频率和收缩力，增加室内传导时间和冠状动脉血流量。这些结果表明，比地索胺在抗心律失常方面与其他I类抗心律失常药物如吡美诺和KW-3401相似，有望成为一种临床有用的抗心律失常药物。
