Antiarrhythmic drug target choices and screening

Abstract

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.