panadiplon and beta-carboline-3-carboxylic-acid-methyl-ester

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.

Topics: Animals; Anti-Anxiety Agents; Binding, Competitive; Brain Chemistry; Carbolines; Cerebellum; Convulsants; Cyclic GMP; Diazepam; Dose-Response Relationship, Drug; Electroshock; Flunitrazepam; Male; Mice; Muscimol; Oxadiazoles; Quinoxalines; Rats; Rats, Inbred Strains; Stress, Psychological