Contrasting regulation by GABA of the displacement of benzodiazepine antagonist binding by benzodiazepine agonists and purines.
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.
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*
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