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 (25 mg/kg) or diazepam (1 mg/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.