Arrhythmia Models for Drug Research: Classification of Antiarrhythmic Drugs

Journal of Pharmacological Sciences

Keitaro Hashimoto¹ 

[1] Professor Emeritus, University of Yamanashi, Japan

关键词: arrhythmia model;    antiarrhythmic drug;    proarrhythmic potential of drugs;    ion channel;    classification;   

DOI  :  10.1254/jphs.CRJ06013X

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(108)Cited-By(9)The aim of this study was to classify antiarrhythmic drugs based on their effectiveness on 6 in vivo arrhythmia models, mainly using dogs. The models were produced by two-stage coronary ligation, digitalis, halothane-adrenaline, programmed electrical stimulation in old myocardial infarction dogs, coronary artery occlusion/reperfusion, or chronic atrioventricular block. Na+-channel–blocking drugs suppressed two-stage coronary ligation and digitalis arrhythmias. Ca2+-channel blockers and β-blockers suppressed halothane-adrenaline arrhythmia. Positive inotropic drugs aggravated halothane-adrenaline arrhythmia, but did not aggravate digitalis arrhythmia. K+-channel blockers suppressed programmed electrical stimulation induced arrhythmia, but induced torsades de pointes type arrhythmia in chronic atrioventricular block dogs and aggravated halothane-adrenaline arrhythmia. Na+/H+-exchange blockers suppressed coronary artery occlusion/reperfusion arrhythmias. This classification may be useful for predicting the clinical effectiveness in the preclinical stage of drug development.

【 授权许可】

Unknown