Felbamate is a subunit selective modulator of recombinant gamma-aminobutyric acid type A receptors expressed in Xenopus oocytes.
Felbamate (2-phenyl-1,3-propanediol dicarbamate) is clinically available for the treatment of refractory epileptic seizures, and is known to modulate several ion channels including gamma-aminobutyric acid type A (GABA(A)) receptors. To determine felbamate subunit selectivity for GABA(A) receptors we expressed 15 different GABA(A) receptor combinations in Xenopus laevis oocytes. Felbamate positively modulated GABA-currents of alpha(1)beta(2)gamma(2S), alpha(1)beta(3)gamma(2S), alpha(2)beta(2)gamma(2S) and alpha(2)beta(3)gamma(2S), whereas felbamate was either ineffective or negatively modulated the other 11 receptor combinations. Regional distributions of GABA(A) receptor subunits suggest that felbamate may differentially modulate distinct inhibitory circuits, a possibility that may have relevance to felbamate efficacy in refractory epilepsies.
Simeone
Timothy A
TA
Interdepartmental Program in Neuroscience, University of Utah, Salt Lake City, UT 84112-9057, USA.
Otto
James F
JF
Wilcox
Karen S
KS
White
H Steve
HS
D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D004274:DNA, Recombinant / Q000008:administration & dosage / Q000235:genetics; D003975:Diazepam / Q000494:pharmacology; D000078328:Felbamate; D005260:Female; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018408:Patch-Clamp Techniques; D048448:Phenylcarbamates / Q000494:pharmacology*; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D011409:Propylene Glycols / Q000494:pharmacology*; D021122:Protein Subunits / Q000235:genetics / Q000502:physiology; D011963:Receptors, GABA-A / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D004274:DNA, Recombinant; D018757:GABA Modulators; D048448:Phenylcarbamates; D011409:Propylene Glycols; D021122:Protein Subunits; D011963:Receptors, GABA-A; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D003975:Diazepam; D000078328:Felbamate