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 antiepileptic agent with a unique structure and mechanism of action, possibly involving binding sites at the N-methyl-D-aspartate receptor (NMDA) complex. 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 orally active at doses between 0.1 and 10 mg/kg. Felbamate also reduced scopolamine and dizocilpine antagonism, but was less potent than SCH 54388, reducing scopolamine-induced deficits at 1 to 3 mg/kg, sc in a dose-dependent manner and reducing deficits induced by dizocilpine at doses of 0.1 and 3 mg/kg, SC. The reduction of dizocilpine-induced deficits by felbamate was not dose dependent. These results suggest that SCH 54388 has a mechanism of action involving either directly or indirectly, glutaminergic and cholinergic central neuronal systems. (C) 1997 Elsevier Science Inc.