Antiarrhythmic drug development: Historical review and future perspective

Cardiac ion channels represent the traditional target for antiarrhythmic drug development. Although channel-selective drugs are effective in treating supraventricular arrhythmias, they are less effective against life-threatening ventricular arrhythmias, and some are proarrhythmic. Paradoxically, the one exception, amiodarone, which uniquely suppresses ventricular fibrillation without proarrhythmia, is one of the least channel-selective drugs currently available (and thus has extracardiac side effects). Thus, antiarrhythmic drug development has become becalmed. This review describes the history of antiarrhythmic drug development, considers antiarrhythmic drugs to date, and provides an overview of current novel therapeutic areas of drug development in an attempt to introduce some of the articles contained within this focused issue of Drug Development Research. Models (for preclinical antiarrhythmic drug assessment) and mechanisms (of drug action and arrhythmia suppression) are the themes of this issue. Drug Dev. Res. 55:3-16, 2002. (C) 2002 Wiley-Liss, Inc.