MECHANISM OF ACTION OF THE ANTICONVULSANT FELBAMATE - OPPOSING EFFECTS ON N-METHYL-D-ASPARTATE AND GAMMA-AMINOBUTYRIC-ACID, RECEPTORS

Felbamate is a promising new antiepileptic drug whose mechanism of act ion is unknown. In whole-cell voltage clamp recordings from cultured r at hippocampal neurons, clinically relevant concentrations of felbamat e (0.1-3 mM) inhibited N-methyl-D-aspartate (NMDA) responses and poten tiated gamma-aminobutyric acid (GABA) responses. Single-channel record ings indicated that the effect on NMDA responses occurred via a channe l blocking mechanism. Felbamate is the first anticonvulsant drug with dual action on excitatory (NMDA) and inhibitory (GABA) brain mechanism s. This unique combination of effects could account for felbamate's br oad spectrum of anticonvulsant activity in animal seizure models and i ts distinctive clinical efficacy and safety profile.