Mechanism of action of the anticonvulsant felbamate: Opposing effects on <i>N</i>‐methyl‐<scp>D</scp>‐aspartate and γ‐aminobutyric acid<sub><scp>A</scp></sub> receptors
Annals of NeurologyPublished 1 October 1994
R. Duane Sofia
Citations194
SJR quartileQ1
SJR score3.74
SNIP2.26
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Abstract
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.
Keywords
MedicineNeuroscienceBiochemistry, Genetics and Molecular Biology
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In whole‐cell voltage clamp recordings from cultured rat hippocampal neurons, clinically relevant concentrations of felbamate inhibited N‐methyl‐D‐aspartate (NMDA) responses and potentiated γ‐aminobutyric acid (GABA) responses, indicating that the effect on NMDA responses occurred via a channel blocking mechanism.
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