title: In vivo modulation of benzodiazepine receptor function after inhibition of endogenous gamma-aminobutyyric acid synthesis.
abstract: The influence of decreased endogenous gamma-aminobutyric acid (GABA) concentration on benzodiazepine receptor function was studied in the brain of living baboons. Positron emission tomography and the radiotracer [11C]flumazenil combined with electroencephalography were used to determine the pharmacological properties of two bezodiazepine receptors agonists, diazepam and bretazenil, in baboons pre-treated or not with DL-allylglycine (an inhibitor of GABA synthesis). Our results show that, in vivo, DL-allylglycine reduces the affinity of benzodiazepine receptors for their agonists without altering the intrinsic capability of agonists to allosterically modulate GABAergic transmission.
authors.affiliation: CEA, DRM, DSV, Service Hospitalier Frédéric Joliot, Orsay, France.
authors.forename: M
authors.initials: M
authors.lastname: Bottlaender
authors.forename: L
authors.initials: L
authors.lastname: Schmid
authors.forename: C
authors.initials: C
authors.lastname: Fuseau
authors.forename: D
authors.initials: D
authors.lastname: Fournier
authors.forename: E
authors.initials: E
authors.lastname: Brouillet
authors.forename: M
authors.initials: M
authors.lastname: Mazière
mesh_terms: D000501:Allylglycine / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D003292:Convulsants / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects; D005442:Flumazenil / Q000493:pharmacokinetics; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000493:pharmacokinetics / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D008024:Ligands; D008297:Male; D010215:Papio; D010433:Pentylenetetrazole / Q000494:pharmacology; D014055:Tomography, Emission-Computed; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis*
chemical_list: D003292:Convulsants; D018755:GABA Agonists; D018756:GABA Antagonists; D018757:GABA Modulators; D058785:GABA-A Receptor Agonists; D008024:Ligands; D000501:Allylglycine; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D003975:Diazepam; D010433:Pentylenetetrazole