Felbamate, 2-phenyl-1,3-propanediol dicarbamate, is a novel, orally active anticonvulsant that has recently been approved for the treatment of Lennox-Gastaut syndrome and partial onset seizures in the United States. Felbamate is active in a broad range of animal anticonvulsant tests. Although its mechanism of action has yet to be fully elucidated, felbamate appears to act by inhibiting the spread of seizures and elevating seizure threshold. One proposed mechanism of action for felbamate is via the NMDA receptor complex. Previous studies have demonstrated the ability of felbamate to inhibit glycine binding at the NMDA receptor complex. The present study examined the effects of felbamate on NMDA/glycine-stimulated increases in intracellular calcium (Ca2+) using cultured rat hippocampal neurons. The results of these experiments demonstrate that felbamate inhibits NMDA/glycine-stimulated increases in intracellular Ca2+ with a minimal effective concentration of 100 microM.