The influence of
1-(2-trifluoromethylphenyl)imidazole (TRIM) and
3-bromo-7-nitroindazole (3-Br-7-NI), potent and relatively selective inhibitors of neuronal
nitric oxide (
NO) synthase, on the antinociceptive and anticonvulsive effects of
diazepam and
clonazepam was investigated in mice. The effects were assessed in the writhing test and
pentetrazole-induced
seizures, respectively. The antinociceptive effects of the threshold doses of
diazepam (1 mg/kg) and
clonazepam (0.0375 mg/kg) were significantly increased by TRIM (7.5 mg/kg) but not by
3-Br-7-NI (10 mg/kg).
L-arginine (125 mg/kg) was able to reverse the effects produced by co-administration of TRIM (7.5 mg/kg) with
diazepam (1 mg/kg), and also of TRIM (7.5 mg/kg) with
clonazepam (0.0375 mg/kg). Protective efficacy of the threshold dose (0.05 mg/kg) of
diazepam against
pentetrazole-induced tonic convulsions and death was significantly increased by TRIM (25 mg/kg) but not by
3-Br-7-NI (10 and 100 mg/kg). TRIM (25 mg/kg) intensified the protective efficacy of the threshold dose (0.005 mg/kg) of
clonazepam, but the effect was not reversed by
L-arginine (125 mg/kg). The present results seem to confirm, at least partly, participation of NO in antinociceptive and
anticonvulsant effects of
benzodiazepines, and point to TRIM as a better tool than 3-Br-7NI for examination of the role of NO in behavioral studies.