REDUCTION OF DIZOCILPINE AND SCOPOLAMINE-INDUCED DEFICITS IN AVOIDANCE RESPONDING BY SCH-54388, A METABOLITE OF FELBAMATE

Felbamate (2-phenyl-1,3-propanediol dicarbamate) is a novel antiepilep tic agent with a unique structure and mechanism of action, possibly in volving binding sites at the N-methyl-D-aspartate receptor (NMDA) comp lex. A monocarbamate metabolite of felbamate (SCH 54388) was compared to felbamate using a mouse passive-avoidance paradigm (PAR). SCH 54388 was markedly free of toxic side effects up to doses of 300 mg/kg, sc. SCH 54388 reduced the deficit-producing effects of either scopolamine , a cholinergic antagonist, or dizocilpine (MK-801), an NMDA receptor channel blocker, in a dose-dependent manner. The effective dose range of SCH 54388 was between 0.01 and 10 mg/kg, sc, SCH 54388 was also ora lly active at doses between 0.1 and 10 mg/kg. Felbamate also reduced s copolamine and dizocilpine antagonism, but was less potent than SCH 54 388, reducing scopolamine-induced deficits at 1 to 3 mg/kg, sc in a do se-dependent manner and reducing deficits induced by dizocilpine at do ses of 0.1 and 3 mg/kg, SC. The reduction of dizocilpine-induced defic its by felbamate was not dose dependent. These results suggest that SC H 54388 has a mechanism of action involving either directly or indirec tly, glutaminergic and cholinergic central neuronal systems. (C) 1997 Elsevier Science Inc.