Electrophysiological effects of risperidone in mammalian cardiac cells.
In this study, the effects of risperidone, the widely used antipsychotic drug, on isolated canine ventricular myocytes and guinea-pig papillary muscles were analyzed using conventional microelectrode and whole cell voltage-clamp techniques. Risperidone concentration-dependently lengthened action potential duration in guinea-pig papillary muscles (EC(50)=0.29+/-0.02 micro M) and single canine ventricular myocytes (EC(50)=0.48+/-0.14 micro M). This effect was reversible, showed reverse rate dependence, and it was most prominent on the terminal portion of repolarization. No significant effect of risperidone on the resting membrane potential, action potential amplitude or maximum rate of depolarization was observed. In voltage-clamped canine ventricular myocytes risperidone caused concentration-dependent block of the rapid component of the delayed rectifier K(+) current ( I(Kr)), measured as outward current tails at -40 mV, with an IC(50) of 0.92+/-0.26 micro M. Suppression of I(Kr) was not associated with changes in activation or deactivation kinetics. High concentration of risperidone (10 micro M) suppressed also the slow component of the delayed rectifier K(+) current ( I(Ks)) by 9.6+/-1.5% at +50 mV. These effects of risperidone developed rapidly and were readily reversible. Risperidone had no significant effect on the amplitude of other K(+) currents ( I(K1) and I(to)). The inhibition of cardiac I(Kr) current by risperidone may explain the cardiac side-effects observed occasionally with the drug. Our results suggest that risperidone displays class III antiarrhythmic properties, and as such, may produce QTc prolongation, especially in patients with long QT syndrome. Therefore, in psychotic patients having also cardiac disorders, ECG control may be suggested during risperidone therapy.
Magyar
János
J
Department of Physiology, University Medical School of Debrecen, 4012 Debrecen, P.O. Box 22, Hungary.
Bányász
Tamás
T
Bagi
Zsolt
Z
Pacher
Pál
P
Szentandrássy
Norbert
N
Fülöp
László
L
Kecskeméti
Valéria
V
Nánási
Péter P
PP
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D010210:Papillary Muscles / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018967:Risperidone / Q000494:pharmacology*
D018967:Risperidone