Neostigmine, but not Metoclopramide, Abolishes Ethosuximide-Induced Functional Gastrointestinal Disturbances

Abstract

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.

First evidence of altered microbiota and intestinal damage and their link to absence epilepsy in a genetic animal model, the WAG/Rij rat

“…This latter organism is known to convert succinate to propionic acid, and both have been suggested as messengers inside the GMB axis 50 ; however, their role in absence seizures and epilepsy should be further investigated, and other studies are needed in this model to understand which may be the most important mediators involved in the link between gut microbiota and epilepsy. In any case, the positive effect of FMT from ETH‐treated rats also suggests that part of ETH action may be mediated by its effects on gut microbiota, and although no data in this direction are available, ETH side effects on the gastrointestinal tract are well known and may share common mechanisms; ETH has been reported to modify intestinal motility, which may per se have an effect on gut microbiota composition 51 …”

Ethosuximide converts ictogenic neurons initiating absence seizures into normal neurons in a genetic model

“…However, it is plausible that the membrane hyperpolarization, and the associated decrease in spontaneous and current‐evoked firing rate, found in deep‐layer neurons of the focal region after ETX treatment are caused, at least in part, by a reduction of I Na P . Indeed, ETX induces in vitro a robust hyperpolarization in gastrointestinal smooth muscle cells (Sirakov et al., 2005), reduces I Na P in layer V cortical neurons (Crunelli & Leresche, 2002), and is responsible for a small membrane hyperpolarization in a subset of thalamic neurons (Leresche et al., 1998). It is likely that the anti‐absence action of phenytoin, when locally applied in the cortical focus of WAG/Rij rats (Gurbanova et al., 2006), results from similar alteration in the activity of cortical focus neurons via an inhibition of voltage‐sensitive sodium channels (Tunnicliff, 1996).…”

Global Small Bowel Motility: Assessment with Dynamic MR Imaging

“…For prokinesis, we administered neostigmine, which has a demonstrated stimulatory effect in vivo (3,(18)(19)(20). Although 2 mg has been shown to exert a prokinetic effect in chronic intestinal pseudoobstruction, we wanted to minimize the chance of adverse effects and thus chose 0.5 mg-concordant with that used by Serrea et al (3) and Ponec et al (21).…”