New class III antiarrhythmic drugs.

Abstract

Several new antiarrhythmic compounds with pure class III activity are currently under development and seem to possess considerable antiarrhythmic potential. The primary electrophysiological action of class III agents is selective prolongation of repolarization without conduction slowing. This effect is usually mediated by block of one or more potassium currents which results in prolongation of the action-potential duration and refractoriness in both atrial and ventricular myocardium. The magnitude of increases in effective refractory period decreases as the heart rate is increased, i.e. these drugs display 'reverse use-dependence'. Initial animal and clinical studies have shown that class III agents are effective against re-entrant supraventricular and ventricular arrhythmias without having any important negative inotropic effect in the compromised ventricle. Animal studies have also suggested that these drugs may be useful in suppressing postinfarction arrhythmias and preventing arrhythmic sudden death. However, concerns have been raised by reports of substantial proarrhythmic tendency associated with these drugs, mainly in the form of torsade de pointes. Careful clinical evaluation is required to establish the clinical benefits of these potentially promising new compounds.