In vivo modulation of benzodiazepine receptor function after inhibition of endogenous gamma-aminobutyyric acid synthesis.
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.
Bottlaender
M
M
CEA, DRM, DSV, Service Hospitalier Frédéric Joliot, Orsay, France.
Schmid
L
L
Fuseau
C
C
Fournier
D
D
Brouillet
E
E
Mazière
M
M
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*
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