Novel targets for cardiac antiarrhythmic drug development.
Cardiac arrhythmias remain a major source of morbidity and mortality in developed countries. Antiarrhythmic drug therapy was traditionally the mainstay of cardiac arrhythmia treatment; however, drug therapy of cardiac arrhythmias has been plagued by incomplete efficacy and by potentially serious adverse reactions, of which the most worrisome has been a potential for malignant proarrhythmia and related effects to increase cardiac mortality. This article reviews the principal arrhythmia mechanisms and their ionic determinants, and discusses potential innovative approaches to new antiarrhythmic drug development, including the consideration of novel ionic targets, potential biophysical approaches and non-channel components involved in composing the arrhythmic substrate.
Department of Pharmacology and Therapeutics, McGill University and Research Center.
John Christian
JC
Hesketh
Daniel
D
Herrera
Stephen
S
Zicha
Stanley
S
Nattel
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000503:physiopathology; D015195:Drug Design; D006801:Humans; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000502:physiology; D013678:Technology, Pharmaceutical / Q000379:methods / Q000639:trends
D000889:Anti-Arrhythmia Agents; D007473:Ion Channels