Ucb L059, a novel anti-convulsant drug: pharmacological profile in animais

Abstract

The anticonvulsant activity of uch L059 ((S)-α-cthyl-2-oxo-pyrrolidinc acetamide) was evaluated in a range of animal models, uch L059 was active after oral and intraperitoneal administration in both rats and mice, with a unique profile of action incorporating features in common with several different types of anticpilcptic drugs. The compound was active, with ED 50 values generally within the range of 5.0–30.0 mg/kg, in inhibiting audiogcnic seizures, electrically induced convulsions and convulsions induced chemically by pentylenetetra Me (PTZ), bicucullinc, picrotoxin and N-methyl-D-aspartate (NMDA). ucb L059 retarded the development of PTZ-induced kindling in mice and reduced PTZ-induced EEG spike ways discharge in rats. The R enantiomer, ucb L060, had low intrinsic anticonvulsant activity, showing the stereospecificity of action of the molecule although the actual mechanism of action remains unknown. Ncurotoxicity, evaluated with an Irwin-type observation test, the rotarod test and open-field exploration, was minimal, with only mild sedation being observed, even at doses 50–100 times higher than the anticonvulsant doses; at pharmacologically active doses, the animals appeared calm but slightly more active, ucb L059 thus presents as an orally active, safe, broad-spectrum anticonvulsant agent, with potential anticpileptogenic and anti-absence actions.