Gluais Pascale, Bastide Michèle, Caron Jacques, Adamantidis Monique
Laboratoire de Pharmacologie, Faculté de Médecine Henri Warembourg, Pole Recherche, 1 place de Verdun, 59045 Lille Cedex, France.
Eur J Pharmacol. 2002 May 31;444(3):123-32. doi: 10.1016/s0014-2999(02)01626-6.
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.
抗精神病药物导致QT间期延长是一种不良副作用，可能会引发室性心律失常。抗精神病药物利培酮已被证明会导致QT间期延长，尤其是在过量用药的情况下。我们研究了利培酮对从兔浦肯野纤维和心室心肌记录的动作电位以及从兔心房和心室分离的心肌细胞记录的钾电流的影响。结果表明：（1）利培酮（0.1 - 3微摩尔）对两种组织的动作电位持续时间都有显著的延长作用，对浦肯野纤维的作用更强，并且在低刺激频率下会引发早期后去极化；（2）利培酮（0.03 - 0.3微摩尔）显著降低延迟整流电流的电流密度，在30微摩尔时会降低瞬时外向电流和内向整流电流。本研究可能解释了在一些使用利培酮治疗的患者中观察到的QT间期延长现象，并为心脏不良事件的风险提供了启示。
