Risperidone prolongs cardiac action potential through reduction of K+ currents in rabbit myocytes.
Prolongation of QT interval by antipsychotic drugs is an unwanted side effect that may lead to ventricular arrhythmias. The antipsychotic agent risperidone has been shown to cause QT prolongation, especially in case of overdosage. We investigated risperidone effects on action potentials recorded from rabbit Purkinje fibers and ventricular myocardium and on potassium currents recorded from atrial and ventricular rabbit isolated myocytes. The results showed that (1) risperidone (0.1-3 microM) exerted potent lengthening effects on action potential duration in both tissues with higher potency in Purkinje fibers and caused the development of early afterdepolarizations at low stimulation rate; (2) risperidone (0.03-0.3 microM) reduced significantly the current density of the delayed rectifier current and at 30 microM decreased the transient outward and the inward rectifier currents. This study might explain QT prolongation observed in some patients treated with risperidone and gives enlightenment on the risk of cardiac adverse events.
Gluais
Pascale
P
Laboratoire de Pharmacologie, Faculté de Médecine Henri Warembourg, Pole Recherche, 1 place de Verdun, 59045 Lille Cedex, France. pascale_gluais@yahoo.fr
Bastide
Michèle
M
Caron
Jacques
J
Adamantidis
Monique
M
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism* / Q000502:physiology; D011690:Purkinje Fibers / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D018967:Risperidone / Q000494:pharmacology*; D016276:Ventricular Function
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D018967:Risperidone