RP 58866 and its active enantiomer RP 62719 (terikalant): blockers of the inward rectifier K+ current acting as pure class III antiarrhythmic agents.
The present article presents an overview of the pharmacologic profile of the benzopyran derivative RP 58866, a racemic mixture, and of RP 62719 (terikalant), its active enantiomer. In normal cardiac tissues studied in vitro, both drugs dose-dependently prolonged the atrial and ventricular action potential but affected neither the upstroke of the action potential nor the diastolic potential. Patch-clamp experiments demonstrated that the prolongation of the action potential induced by the drugs is due to a specific blockade of the inward rectifier K+ current. In vivo, intravenous administration to anesthetized dogs of low doses of RP 62719 consistently induced bradycardia and prolonged the atrial, nodal, and ventricular refractory periods, but did not affect the conduction velocity. Because of these properties, RP 58866 and RP 62719 exert potent antiarrhythmic and antifibrillatory actions both at the atrial and ventricular levels in various experimental models of arrhythmia. Our results demonstrate that RP 58866 and RP 62719 are K(+)-channel blockers acting as pure class III antiarrhythmic drugs.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy; D001578:Benzopyrans; D002839:Chromans; D002867:Chromones / Q000494:pharmacology*; D004594:Electrophysiology; D006801:Humans; D008955:Models, Cardiovascular; D010880:Piperidines / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*
D000889:Anti-Arrhythmia Agents; D001578:Benzopyrans; D002839:Chromans; D002867:Chromones; D010880:Piperidines; D015221:Potassium Channels; C063899:terikalant