US EPA

3234146 

Journal Article 

Role of nitric oxide in anticonvulsant effects of benzodiazepines in mice 

Talarek, S; Fidecka, S 

2003 

1 

Polish journal of pharmacology
ISSN: 1230-6002 

55 

2 

181-191 

WOS:000183086900007 

The influence of nitric oxide (NO) on anticonvulsant
activity of diazepam and clonazepam was examined in the pentetrazole- and electroshock-induced
seizure models in mice. Protective efficacy of the threshold dose of diazepam against
pentetrazole-induced clonic and tonic seizures, and death was significantly increased by N-G-
nitro-L-arginine methyl ester hydrochloride (L-NAME) while 7-nitroindazole (7-NI) was slightly
less effective. The above intensifying effect of L-NAME on antiepileptic activity of diazepam was
reversed by L-arginine, a substrate for NO formation, but not by D-arginine. Methylene blue, the
guanylate cyclase inhibitor, increased the protective efficacy of diazepam and clonazepam in the
pentetrazole-induced seizures. 7-NI was able to potentiate the protective efficacy of diazepam
and clonazepam in electroshock-induced tonic hindlimb extension. These findings suggest that the
cGMP/NO system may participate in antiepileptic effects of benzodiazepines. 

nitric oxide; benzodiazepines; seizures; mice