Mechanism of action of the anticonvulsant felbamate: Opposing effects on N-methyl-D-aspartate and γ-aminobutyric acidA receptors

Jong M. Rho, Sean D. Donevan, Michael A Rogawski

Research output: Contribution to journalArticle

198 Scopus citations


Felbamate is a promising new antiepileptic drug whose mechanism of action is unknown. In whole-cell voltage clamp recordings from cultured rat hippocampal neurons, clinically relevant concentrations of felbamate (0.1-3 mM) inhibited N-methyl-D-aspartate (NMDA) responses and potentiated γ-aminobutyric acid (GABA) responses. Single-channel recordings indicated that the effect on NMDA responses occurred via a channel blocking mechanism. Felbamate is the first anticonvulsant drug with dual actions on excitatory (NMDA) and inhibitory (GABA) brain mechanisms. This unique combination of effects could account for felbamate's broad spectrum of anticonvulsant activity in animal seizure models and its distinctive clinical efficacy and safety profile.

Original languageEnglish (US)
Pages (from-to)229-234
Number of pages6
JournalAnnals of Neurology
Issue number2
StatePublished - Feb 1994
Externally publishedYes


ASJC Scopus subject areas

  • Neuroscience(all)

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