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| Abstracts |
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IJPP
2003; 47 (4) : 400 - 406
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Effect
of 7-nitroindazole alone and in combination
with phenobarbitone and diazepam on picrotoxin-
induced convulsions in rats
Vanaja Paul* and P. Ekambaram
Departments of *Pharmacology and Environmental Toxicology,
Dr. ALM Postgraduate Institute of Basic Medical Sciences,
University of Madras,
Taramani, Chennai 600 113
( Received on May 28, 2003 )
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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.
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