Effect of 7-nitroindazole alone and in combination with phenobarbitone and diazepam on picrotoxin-induced convulsions in rats.
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.
Paul
Vanaja
V
Department of Pharmacology, Dr. ALM Postgraduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai 600 113.
Ekambaram
P
P
D000818:Animals; D003975:Diazepam / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D007191:Indazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D010634:Phenobarbital / Q000627:therapeutic use*; D010852:Picrotoxin / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*
D003975:Diazepam; D007191:Indazoles; D010634:Phenobarbital; D010852:Picrotoxin; C080122:7-nitroindazole