Effect of 7-nitroindazole Alone and in Combination With Phenobarbitone and Diazepam on Picrotoxin-Induced Convulsions in Rats

Vanaja Paul, P Ekambaram

Indian J Physiol Pharmacol. 2003 Oct;47(4):400-6.

PMID: 15266951

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP2942429	7-Nitroindazole		2942-42-9	Price