MPEP, an antagonist of metabotropic glutamate receptors, exhibits anticonvulsant action in immature rats without a serious impairment of motor performance

An antagonist of type I metabotropic glutamate receptors MPEP was found to exhibit anticonvulsant action in adult rodents. Present experiments were focused on action of this drug against pentetrazol-induced motor seizures in immature rats 12-, 18-and 25-days old. Dose of pentetrazol (100 mg/kg s.c.) was chosen to elicit minimal clonic seizures and (after a longer latency) generalized tonic-clonic seizures. Pretreatment with MPEP (doses from 10 to 80 mg/kg i.p.) resulted in a dose-dependent suppression of the tonic phase of generalized tonic-clonic seizures in all age groups studied. Efficacy of MPEP was higher and the effect lasted longer in 12- than in 25-day-old rats. In addition, minimal clonic seizures were suppressed in 18-day-old rats. Motor abilities of immature animals were not compromised by MPEP in doses of 20 and/or 40 mg/kg i.p., only righting reflex was a little slowed down in 12- and 18-day-old rats. In contrast to antagonists of ionotropic glutamate receptors anticonvulsant doses of MPEP do not induce unwanted side effects in motor performance of developing rats. (C) 2004 Elsevier B.V. All rights reserved.