Future of antiarrhythmic drugs.
OBJECTIVE
This article briefly summarizes the principal mechanisms of action of contemporary antiarrhythmic agents, delineates their limitations in the treatment of cardiac arrhythmias, and discusses why there is a need for new cardiac antiarrhythmic drugs.


RESULTS
In recent years, the limited efficacy and proarrhythmic potential of classic antiarrhythmic drugs have focused attention on nonpharmacologic approaches to treatment of cardiac arrhythmias. Despite the current success of ablative therapy and implantable defibrillators, the need is still pressing for new antiarrhythmic drugs. Evolving knowledge about the molecular mechanisms of cardiac arrhythmias provides innovative strategies for discovering new cardiac antiarrhythmic drugs. Some of these have already led to the development of new compounds on the verge of clinical use, and others hold great promise for future drug development.


CONCLUSIONS
Cardiac arrhythmias are associated with significant morbidity and mortality in developed countries. Antiarrhythmic drug therapy was traditionally the mainstay of arrhythmia treatment; however, the inefficacy of drug treatment and the potential that antiarrhythmic drugs can provoke life-threatening arrhythmias have generated interest in new approaches to antiarrhythmic drug development. Improved understanding of the cellular and molecular basis of cardiac arrhythmias holds the promise of identifying novel approaches for the treatment of cardiac arrhythmias. These approaches may target traditional and newly discovered cardiac ion channels, as well as new molecular and signaling pathways that modulate arrhythmic substrates.
Darbar
Dawood
D
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Roden
Dan M
DM
D000889:Anti-Arrhythmia Agents / Q000145:classification / Q000494:pharmacology* / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000187:drug effects; D015195:Drug Design; D006329:Heart Conduction System / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D013678:Technology, Pharmaceutical / Q000639:trends
D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D007473:Ion Channels