比较奎尼丁,E-4031对大鼠和豚鼠药物诱发心律失常模型的作用  

Comparison of effects of quinidine and E4031 on aconitine and strophantin G induced cardiac arrhythmia in rats and guinea pigs

作　　者：张琼[1] 王晓良[1] 

机构地区：[1]中国医学科学院

出　　处：《中国药理学与毒理学杂志》1998年第3期181-183,共3页Chinese Journal of Pharmacology and Toxicology

基　　金：国家杰出青年科学基金

摘　　要：通过整体动物实验，探讨具有钾通道亚型选择性的奎尼丁和Ｅ－４０３１，与抗心律失常作用的关系．本实验选择了具有不同钾离子通道特性的动物模型．由于动物的种属差异，采取乌头碱诱发大鼠心律失常，毒毛花甙Ｇ诱发豚鼠心律失常的经典方法，观察了Ｉａ类抗心律失常药物奎尼丁和Ⅲ类药Ｅ－４０３１在这两种动物模型上的作用．实验结果表明，奎尼丁１０ｍｇ·ｋｇ－１可明显抑制大鼠的心律失常，但３０μｇ·ｋｇ－１的Ｅ－４０３１无效，而在豚鼠模型上，３μｇ·ｋｇ－１的Ｅ－４０３１即可抑制室性早搏的出现，奎尼丁３０ｍｇ·ｋｇ－１才出现抑制作用．The purpose of this study was to investigate the relationship between the K^+ channel subtype selectivity and antiarrhythmic effects of quinidine and E4031 N(4-[(1-[2-(6-methyl-2-pyridyl)ethyl]-4-piperidyl)-carbonyl]-phenyl)methanesulfonamide dihydrochloride dihydrate]. In comparison with the effects of quinidine (antiarrhythmic agents with Ito blockade) and E4031 (a potent Ik blocker) on aconitine induced cardiac arrhythmia in rats and strophantin G induced arrhythmia in guinea pigs. The results showed that quinidine was effective to prevent against arrhythmia in rats at dose of 10 mg·kg1, E4031 was not effective at the dose of 30 μg·kg1. However, in guinea pigs, E4031 was effective at the dose of 3 μg·kg1. Quinidine was not effective till at higher dose of 30 mg·kg1. The results suggest that the different effects of these two drugs on the two animal models are related to their channel subtype selectivity and implies that the cardiac Ito may be a target of some antiarrhythmia agents. 

关 键 词：奎尼丁 E-4031 抗心律失常药 钾通道 

分 类 号：R972.2[医药卫生—药品]