Involvement of nitricoxidergic system in the hypnotic effects of benzodiazepines in mice

The influence of nitric oxide (NO) on hypnotic activity of diazepam, chlordiazepoxide and clonazepam was studied in mice. Administration of both non-selective NO synthase inhibitors: N-G-nitro-L-arginine methyl ester (L-NAME), N-G-nitro-L-arginine (L-NOARG) and selective NO synthase inhibitor 7-nitroindazole (7-NI) resulted in significant increase in the duration of diazepam-, chlordiazepoxide- and clonazepam-induced sleep. The effects of co-administration of the examined inhibitors with benzodiazepines were not changed by L-arginine, a substrate for NO formation. Administration of L-arginine alone had no effect on the duration of sleep induced by benzodiazepines. Methylene blue, the guanyl cyclase inhibitor, was able to increase the duration of benzodiazepine-induced sleep. These findings suggest that the cGMP/NO system may participate in hypnotic effects of benzodiazepines.