Cardiac electropharmacological effects of an antidiarrheal drug loperamide and its antidote naloxone were assessed in isoflurane-anesthetized guinea pigs. Intravenous administration of loperamide at 0.01-0.1 mg/kg did not affect parameters of electrocardiogram (ECG) or monophasic action potential (MAP) of the right ventricle. Additional administration of loperamide at 1 mg/kg prolonged the QT interval and MAP duration of the ventricle accompanied with increments of the PQ interval and QRS width. The potency of loperamide for QT-interval prolongation was about 100-times lower than that of dofetilide, in spite that similar inhibitory effects on the human Ether-a-go-go Related Gene (hERG) K+ channels have been reported between loperamide and dofetilide, implying lower accessibility of loperamide to the K+ channels. Intravenous administration of naloxone at 0.003-0.3 mg/kg, which effectively inhibits µ-opioid receptors, did not affect ECG parameters including QT interval or MAP duration. Furthermore, the loperamide-induced cardiac electrophysiological changes were not modified in the presence of naloxone at 0.3 mg/kg. These results suggest that loperamide has a potential to delay cardiac conduction and repolarization in the in vivo condition. Since naloxone did not modify ECG parameters and loperamide-induced ECG changes, naloxone is confirmed to possess acceptable cardiac safety when used as an antidote.
Keywords: QT interval; loperamide; monophasic action potential; naloxone.