γ-Aminobutyric Acid and Pentobarbital Enhance 2-[3H]Oxoquazepam Binding to Type I Benzodiazepine Recognition Sites in Rat and Human Brain

2-Oxoquazepam (2oxoquaz) is a novel benzodiazepine which shows preferential affinity for type I benzodiazepine recognition sites. In the present study, we analyzed the effect of gamma-aminobutyric acid (GABA), pentobarbital, and chloride ions on 3H]2oxoquaz and 3H]flunitrazepam ( 3H]FNT) binding to membrane preparations from rat and human brain. GABA stimulated 3H]-2oxoquaz and 3H]FNT binding in a concentration-dependent manner. The maximal enhancement produced by GABA on 3H]2oxoquaz binding was higher than that produced on 3H]FNT binding in both rat and human tissues. In the rat brain, the effect of GABA on 3H]2oxoquaz was similar throughout different brain areas, whereas the effect on 3H]FNT binding was lower in the cerebral cortex and hippocampus than in the cerebellum. Moreover, both 3H]2oxoquaz and 3H]FNT binding were stimulated by chloride ions and pentobarbital. The results are consistent with the hypothesis that type I benzodiazepine recognition sites are linked functionally to the GABA recognition site and the chloride ionophore.