Neostigmine, but not metoclopramide, abolishes ethosuximide-induced functional gastrointestinal disturbances

Ethosuximide is a drug used for the treatment of absence seizures. Its prolonged application leads to gastrointestinal (GI) disturbances. The purpose of the present study was to determine the severity and nature of the disturbances, as well as the influence exerted upon them by neostigmine methylsulfate and metoclopramide. The drug-induced alterations, occurring in the rat GI tract, were registered by X-ray contrast examination. In vitro experiments were carried out on isolated GI smooth muscle (SM) preparations. The latter revealed that the drug hyperpolarized the SM tissues and inhibited their contractile activity. X-rays of ethosuximide-treated rats showed GI hypotonia, disturbed peristalsis and decreased evacuation activity. The inhibition of the GI functions was associated with hyperpolarization of SM and a reduction in Ca2+ influx, ensuring spontaneous contractile activity. The application of neostigmine methylsulfate significantly removed ethosuximide-induced functional GI disturbances in rats treated for 15 days with ethosuximide. Copyright (C) 2005 S. Karger AG, Basel.