Characterization of 3H-2-oxo-quazepam binding in the human brain.

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.