THE EFFECT OF THE DESGLYCINYL METABOLITE OF REMACEMIDE ON CORTICAL WEDGES PREPARED FROM DBA 2 MICE/

Remacemide hydrochloride is currently undergoing clinical trials for u se as an anticonvulsant agent in the treatment of epilepsy. It is cons idered that the desglycinyl metabolite (FPL 12495AA) of the parent com pound accounts for the majority of the anticonvulsant activity. In thi s study we have investigated the effects of FPL 12495AA on electrical activity in the cortical wedges prepared from audiogenic seizure-prone DBA/2 mice. FPL 12495AA at varying concentrations (50-200 mu M) signi ficantly reduced both the spontaneous depolarizations (IC50 102 mu M) and the associated afterpotentials (IC50 50 mu M) which are characteri stic in this preparation under magnesium-free conditions. The compound also concentration-dependently reduced N-methyl-D-aspartate (NMDA)-in duced depolarizations of the tissue (IC50 43 mu M) and the antagonism by FPL 12494AA was not overcome by increasing NMDA concentrations. FPL 12495AA had no effect on (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazo le propionic acid (AMPA)-induced depolarizations. The results suggest that FPL 12495AA has a specific antagonistic effect on the NMDA recept or complex possibly through non-competitive inhibition at the phencycl idine site in the ion channel. Such an action could contribute to its anticonvulsant properties.