title: Contrasting regulation by GABA of the displacement of benzodiazepine antagonist binding by benzodiazepine agonists and purines.
abstract: Gaba increases the potency of the benzodiazepines chlordiazepoxide, clonazepam, diazepam, nitrazepam and oxazepam, and the triazolopyridazine CL 218,872 in displacing specific binding of the benzodiazepine antagonist [3H]Ro 15-1788. In contrast, the potencies of the purines 1-methyl- and 1-ethylisoguanosine for benzodiazepine antagonist binding sites were decreased by GABA, while the potencies of inosine, hypoxanthine, 6-dimethylaminopurine, and the non-benzodiazepine anxiolytic, zopiclone, were unaltered by GABA. The results suggest that the purines and 'classical' benzodiazepine agonists may bind to different conformations or populations of receptors.
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000378:metabolism; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D005442:Flumazenil; D011687:Purines / Q000494:pharmacology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects; D011955:Receptors, Drug / Q000187:drug effects* / Q000378:metabolism; D011963:Receptors, GABA-A; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D014151:Anti-Anxiety Agents; D001570:Benzodiazepinones; D011687:Purines; D011956:Receptors, Cell Surface; D011955:Receptors, Drug; D011963:Receptors, GABA-A; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid