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

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10 mg·kg^-1可明显抑制大鼠的心律失常, 但30 μg·kg^-1 的E-4031无效, 而在豚鼠模型上, 3 μg·kg^-1 的E-4031即可抑制室性早搏的出现, 奎尼丁30 mg·kg^-1才出现抑制作用. 推测两种药物的作用与它们对钾通道亚型的选择性有关.

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

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.