title: A microPET comparison of the effects of etifoxine and diazepam on [(11)C]flumazenil uptake in rat brains.
abstract: Using positron emission tomography (PET), the present study assessed the binding of [(11)C]flumazenil to GABA-A receptors in anesthetized rats following a single intravenous injection of an active dose of either etifoxine (25mg/kg) or diazepam (1mg/kg), which are both anxiolytic drugs. [(11)C]flumazenil binding was measured in five discrete brain structures, namely the caudate putamen, hippocampus, cerebellum, occipital cortex and parietal cortex. As expected, diazepam injection produced a significant decrease in [(11)C]flumazenil binding, which was interpreted as benzodiazepine GABA-A receptor occupancy, whereas etifoxine increased the binding of [(11)C]flumazenil. This first use of in vivo imaging after etifoxine administration revealed the activated binding pattern of [(11)C]flumazenil and highlighted the pharmacological differences between etifoxine and benzodiazepines. Using the same [(11)C]flumazenil radiotracer, PET neuroimaging could be applied to larger animals and, ultimately, to human subjects, thus providing new perspectives for better defining the molecular pharmacology of etifoxine.
authors.affiliation: CERMEP-Imagerie du Vivant, Imaging Platform, Bron, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bouillot
authors.affiliation: CERMEP-Imagerie du Vivant, Imaging Platform, Bron, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bonnefoi
authors.affiliation: CERMEP-Imagerie du Vivant, Imaging Platform, Bron, France.
authors.forename: François
authors.initials: F
authors.lastname: Liger
authors.affiliation: CERMEP-Imagerie du Vivant, Imaging Platform, Bron, France; Université Claude Bernard Lyon 1, CNRS, INSERM, Lyon Neuroscience Research Center, Lyon, France; Hospices Civils de Lyon, Lyon, France. Electronic address: luc.zimmer@univ-lyon1.fr.
authors.forename: Luc
authors.initials: L
authors.lastname: Zimmer
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000378:metabolism / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D002247:Carbon Isotopes; D003975:Diazepam / Q000494:pharmacology*; D005442:Flumazenil / Q000493:pharmacokinetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D010078:Oxazines / Q000378:metabolism / Q000494:pharmacology*; D049268:Positron-Emission Tomography; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*
chemical_list: D014151:Anti-Anxiety Agents; D002247:Carbon Isotopes; D010078:Oxazines; D019275:Radiopharmaceuticals; D011963:Receptors, GABA-A; D005442:Flumazenil; D003975:Diazepam; C002125:etifoxine
keywords: Allosteric site; Anxiolytic drug; GABA; Rodent