title: Felbamate is a subunit selective modulator of recombinant gamma-aminobutyric acid type A receptors expressed in Xenopus oocytes.
abstract: 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.
authors.affiliation: Interdepartmental Program in Neuroscience, University of Utah, Salt Lake City, UT 84112-9057, USA.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Simeone
authors.forename: James F
authors.initials: JF
authors.lastname: Otto
authors.forename: Karen S
authors.initials: KS
authors.lastname: Wilcox
authors.forename: H Steve
authors.initials: HS
authors.lastname: White
mesh_terms: 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
chemical_list: 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