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(Circulation Research. 2003;93:491.)
© 2003 American Heart Association, Inc.

Review

Antiarrhythmic Drug Target Choices and Screening

Michael C. Sanguinetti, Paul B. Bennett

From the Department of Physiology (M.C.S.), Eccles Institute of Human Genetics, University of Utah, Salt Lake City, Utah, and the Department of Molecular Pharmacology (P.B.B.), Merck Research Laboratories, West Point, Pa.

Correspondence to Michael Sanguinetti, PhD, Department of Physiology, Eccles Institute of Human Genetics, University of Utah, 15 N 2030 E, Room 4220, Salt Lake City, UT 84112. E-mail Michael.sanguinetti{at}hmbg.utah.edu

Eduardo Marbán Gordon Tomaselli Editors
This Review is part of a thematic series on the Biology of Cardiac Arrhythmias, which includes the following articles:

Antiarrhythmic Drug Target Choices and Screening

Ion Channel Protein Processing

Regulation of Expression and Distribution of Ion Channels

Computational Insights: Chaos and Wave Theory

Gene Therapy and Cell Therapy for Cardiac Arrhythmias

Genomics of Sudden Cardiac Death

Inherited Arrhythmogenic Diseases: The Complexity Beyond Monogenic Disorders

This series is in honor of Harry A. Fozzard, 8th Editor of Circulation Research.

Most antiarrhythmic drugs are ion channel blockers, and to date, those tested in large randomized placebo-controlled clinical trials have shown no decrease in mortality outcome. This apparent lack of survival benefit may result from the significant liabilities associated with these agents that offset any long-term benefit. Despite the current success of implantable defibrillators and the future promise of gene therapy, there is still a pressing need for new antiarrhythmic drugs. An improved understanding of cardiac ion channels and novel approaches to target selection and compound screening will provide new opportunities for drug discovery in the near future. Here, we briefly review the multiple mechanisms of arrhythmia, the history of drug failures, and the possibilities that evolving technologies may provide in the search for more efficacious and safer antiarrhythmic drugs.

Key Words: antiarrhythmic drugs • arrhythmia • ion channels

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