Article date: 1991/6/1
PubMed ID: 1682947
Journal name: Pharmacology, biochemistry, and behavior (ISSN: 0091-3057)
The inhibition constant (Ki) of U-78875 was investigated without and with muscimol in the incubation medium using in vitro (3H)-flunitrazepam [(3H)-FNZ] binding to cortical membrane preparation. Also, the effect of U-78875 on cerebellar cyclic 3',5'-guanosine monophosphate (cGMP) was studied in control and stressed (electric footshock) mice. The Ki of U-78875 was 1.56 nM for inhibition of (3H)-FNZ binding. The presence of muscimol (10(-5) M) had no significant effect on the Ki of U-78875. U-78875 and diazepam significantly decreased cerebellar cGMP, and this effect was antagonized by flumazenil. Both U-78875 and diazepam dose-dependently antagonized electric footshock-induced increases in cGMP, and U-78875 was two orders of magnitude more potent in stressed animals as compared to control animals. These biochemical investigations indicate that U-78875 is an agonist of benzodiazepine receptors, and cGMP may mediate its anxiolytic activity.
Author List: Sethy V H, Oien T T
Publication Types: Comparative Study; Journal Article
Substances mentioned in the article: Anti-Anxiety Agents; Carbolines; Convulsants; Oxadiazoles; Quinoxalines; Muscimol; Flunitrazepam; Cyclic GMP; beta-carboline-3-carboxylic acid methyl ester; Diazepam; panadiplon;
Mesh terms: Animals; Anti-Anxiety Agents/pharmacology; Binding, Competitive/drug effects; Brain Chemistry/drug effects; Carbolines/pharmacology; Cerebellum/drug effects; Convulsants/pharmacology; Cyclic GMP/metabolism; Diazepam/pharmacology; Dose-Response Relationship, Drug; Electroshock; Flunitrazepam/metabolism; Male; Mice; Muscimol/pharmacology; Oxadiazoles/pharmacology; Quinoxalines/pharmacology; Rats; Rats, Inbred Strains; Stress, Psychological/metabolism;