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Effect of 7-nitroindazole alone and in combination with phenobarbitone and diazepam on picrotoxin-induced convulsions in rats.

Abstract
There are no reports on the effect of 7-nitroindazole (7-NI) on chemically-induced convulsions. Hence, in the present study, its (100 and 200 mg/kg) action was tested alone and in combination with phenobarbitone (20 mg/kg) and diazepam (0.25 mg/kg) on picrotoxin (PCT)-induced convulsions in rats. The changes produced by 7-NI on nitric oxide synthase (NOS) activity and nitric oxide (NO) concentration were determined in the brain. The effect of 7-NI was tested in L-arginine (1000 mg/kg) pretreated (30 min) animals. The smaller dose (100 mg/kg) of 7-NI did not alter NOS activity and NO concentration, but inhibited PCT-induced convulsions indicating that its anticonvulsant action was devoid of an involvement of NO. But, an inhibition of NOS activity, by a larger (200 mg/kg) dose of it, resulted in a promotion of the convulsant action of PCT and in an impairment of the anticonvulsant effect of both phenobarbitone and diazepam. The proconvulsant action of 7-NI was reverted by L-arginine. These results suggest that 100 and 200 mg/kg of 7-NI produce distinguishable action on PCT-induced convulsions because NOS activity is inhibited by 200 mg/kg and not by 100 mg/kg of it. The results further suggest that NO acts as anticonvulsant and that the NOS inhibitors, like 7-NI, cannot be used as an anticonvulsant either alone or in combination with other anticonvulsants.
AuthorsVanaja Paul, P Ekambaram
JournalIndian journal of physiology and pharmacology (Indian J Physiol Pharmacol) Vol. 47 Issue 4 Pg. 400-6 (Oct 2003) ISSN: 0019-5499 [Print] India
PMID15266951 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Indazoles
  • Picrotoxin
  • Diazepam
  • 7-nitroindazole
  • Phenobarbital
Topics
  • Animals
  • Diazepam (therapeutic use)
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Indazoles (adverse effects, therapeutic use)
  • Male
  • Phenobarbital (therapeutic use)
  • Picrotoxin (toxicity)
  • Rats
  • Rats, Wistar
  • Seizures (chemically induced, prevention & control)

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