Mechanism of action of the anticonvulsant felbamate: opposing effects on N-methyl-D-aspartate and gamma-aminobutyric acidA receptors.
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 gamma-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.
Rho
J M
JM
Neuronal Excitability Section, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892.
Donevan
S D
SD
Rogawski
M A
MA
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004357:Drug Synergism; D000078328:Felbamate; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000187:drug effects* / Q000378:metabolism
D000927:Anticonvulsants; D048448:Phenylcarbamates; D011409:Propylene Glycols; D018079:Receptors, GABA; D016202:N-Methylaspartate; D000078328:Felbamate