title: Characterization of 3H-2-oxo-quazepam binding in the human brain.
abstract: 1. 2-oxo-quazepam (2oxoquaz) is a novel benzodiazepine (BZD) hypnotic containing a trifluoethyl substituent on the ring nitrogen at position 1, which, unlike other BZDs, distinguishes two populations of BZD binding sites. In the present study we characterized the binding of 3H-2oxoquaz to human brain membrane preparations. 2. Self and cross displacement curves for 3H-FNT and 3H-2oxoquaz binding in different brain areas indicate that 2oxoquaz binds with different affinities to two populations of binding sites in the human brain. 3. Competition studies of 3H-2oxoquaz (2 nM) and 3H-FNT (0.5 nM) binding with a series of unlabelled ligands indicate that compounds which preferentially bind to Type I sites are more potent at displacing 3H-2oxoquaz than 3H-FNT from cerebral cortex membrane preparations. 4. The binding of 3H-2oxoquaz is stimulated by gamma-aminobutyric acid (GABA) and pentobarbital in a concentration-dependent manner. 5. The results suggest that in the human brain 3H-2oxoquaz binds with high affinity to a subpopulation of BZD recognition sites (Type I sites) which are functionally linked to the GABA receptor and the chloride ionophore.
authors.affiliation: Department of Experimental Biology, University of Cagliari, Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Corda
authors.forename: O
authors.initials: O
authors.lastname: Giorgi
authors.forename: B M
authors.initials: BM
authors.lastname: Longoni
authors.forename: E
authors.initials: E
authors.lastname: Ongini
authors.forename: S
authors.initials: S
authors.lastname: Montaldo
authors.forename: F
authors.initials: F
authors.lastname: Paribello
authors.forename: G
authors.initials: G
authors.lastname: Biggio
mesh_terms: D000328:Adult; D014151:Anti-Anxiety Agents / Q000378:metabolism*; D001569:Benzodiazepines; D001570:Benzodiazepinones / Q000378:metabolism*; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011963:Receptors, GABA-A / Q000378:metabolism*; D014316:Tritium
chemical_list: D014151:Anti-Anxiety Agents; D001570:Benzodiazepinones; D011963:Receptors, GABA-A; D014316:Tritium; D001569:Benzodiazepines; C039103:2-oxoquazepam