Effects of sodium nitroprusside, a nitric oxide donor, on gamma-aminobutyric acid concentration in the brain and on picrotoxin-induced convulsions in combination with phenobarbitone in rats.
The concentrations of nitric oxide (NO), the neuronal messenger molecule, and gamma-aminobutyric acid (GABA), the inhibitory neurotransmitter, and the activity of gamma-aminobutyric acid transaminase (GABA-T), the enzyme involved in the degradation of GABA, were measured in the brain of rats treated with graded doses (1.25, 2.5, 5.0 mg/kg) of sodium nitroprusside (SNP), the donor of NO. The effect of SNP was tested alone and in combination with phenobarbitone (PB), the GABA potentiating antiepileptic drug, against picrotoxin (PCT) (5 mg/kg)-induced convulsions in rats. The results of these studies showed that NO released from SNP (2.5 mg/kg) had a potential to inhibit GABA-T activity resulting in an increase in the concentration of GABA in the brain. Thus, SNP (2.5 mg/kg) was able to inhibit PCT-induced convulsions and was able to produce an additive anticonvulsant action with PB. However, a much greater increase in the concentration of NO by 5.0 mg/kg of SNP did not change the activity of GABA-T and the concentration of GABA, and promoted the convulsant action of PCT. These results suggest that a moderate increase in the concentration of NO following the administration of its donor SNP (2.5 mg/kg) results in an enhancement of the concentration of GABA in the brain and in an inhibition of PCT-induced convulsions independently and additively with PB and that a marked increase in NO concentration after the administration of a larger dose of SNP (5.0 mg/kg) results in proconvulsant action.
Paul
Vanaja
V
Department of Pharmacology and Environmental Toxicology, Dr. ALM Postgraduate Institute of Basic Medical Sciences, Taramani, University of Madras, Chennai-600 113, India.
Ekambaram
Perumal
P
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology* / Q000627:therapeutic use; D010852:Picrotoxin / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D004338:Drug Combinations; D009569:Nitric Oxide; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D010634:Phenobarbital; D010852:Picrotoxin; D005680:gamma-Aminobutyric Acid