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稠合吲哚化合物(3aR,12R,12aR,12bS)-12-氨基-2,3,3a,4,11,12,12a,12b-八氢-10-羟基异喹啉并[2,1,8-lma]咔唑-5(1H)-酮盐酸盐1.5水合物的抗心律失常和心血管特性

Antiarrhythmic and cardiovascular profiles of the fused indole compound (3aR,12R,12aR,12bS)-12-amino-2,3,3a,4,11,12,12a,12b-octahydro-10-hydrox yisoquino [2,1,8-lma]carbazol-5(1H)-one hydrochloride 1.5 hydrate.

作者信息

Yorikane R, Mizuno H, Itoh Y, Koike H, Miyake S, Shiga H, Kumakura S, Fukami M, Shimoji Y, Hashimoto T

机构信息

Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.

出版信息

Arzneimittelforschung. 1991 Nov;41(11):1130-6.

PMID:1810258
Abstract

Antiarrhythmic and cardiovascular profiles of a fused indole compound, (3aR,12R,12aR,12bS)-12-amino-2,3,3a,4,11,12,12a,12b -octahydro- 10-hydroxyisoquino [2,1,8-lma]carbazol-5(1H)-one hydrochloride 1.5 hydrate (RS-2135, CAS 133775-36-7), were investigated in anesthetized dogs. Class I antiarrhythmic agents such as disopyramide, lidocaine, mexiletine and flecainide were used as reference compounds. RS-2135 exerted more potent antiarrhythmic activity than reference compounds against ouabain-induced arrhythmias in dogs. The onset of action was slow, but the duration of action was longer than with the other compounds tested. The agent suppressed the conduction in the atrium, A-V node and ventricle more markedly than the reference compounds. RS-2135, however, did not change blood pressure and heart rate at a dose 5 times the dose for antiarrhythmic activity and decreased cardiac contractility to a lesser extent than the reference compounds.

摘要

在麻醉犬中研究了一种稠合吲哚化合物(3aR,12R,12aR,12bS)-12-氨基-2,3,3a,4,11,12,12a,12b-八氢-10-羟基异喹啉并[2,1,8-lma]咔唑-5(1H)-酮盐酸盐1.5水合物(RS-2135,CAS 133775-36-7)的抗心律失常和心血管特性。将Ⅰ类抗心律失常药物如丙吡胺、利多卡因、美西律和氟卡尼用作参考化合物。在犬中,RS-2135对哇巴因诱导的心律失常发挥的抗心律失常活性比参考化合物更强。起效缓慢,但作用持续时间比其他受试化合物更长。该药物比参考化合物更显著地抑制心房、房室结和心室的传导。然而,RS-2135在抗心律失常活性剂量5倍的剂量下不改变血压和心率,并且比参考化合物降低心脏收缩力的程度更小。

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