Role of nitric oxide in anticonvulsant effects of benzodiazepines in mice.
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 NG-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.
Talarek
Sylwia
S
Department of Pharmacodynamics, Medical University School, Staszica 4, PL 20-081 Lublin, Poland.
Fidecka
Sylwia
S
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001120:Arginine / Q000494:pharmacology; D002998:Clonazepam / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004597:Electroshock; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010433:Pentylenetetrazole; D012640:Seizures / Q000188:drug therapy / Q000209:etiology
D000927:Anticonvulsants; D007191:Indazoles; D009569:Nitric Oxide; D002998:Clonazepam; D001120:Arginine; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D003975:Diazepam; D008751:Methylene Blue; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester; D010433:Pentylenetetrazole