Effect of systemically administered nitric oxide donor, sodium nitroprusside on picrotoxin-induced convulsions in rats.
Nitric oxide (NO), the gaseous neurotransmitter has been reported to have an endogenous anticonvulsant property. This has prompted proposals to develop NO donors as anticonvulsant drugs. In the present study, the effect of NO donor, sodium nitroprusside (SNP) on picrotoxin (PCT)-induced convulsions was investigated. A convulsant dose of PCT (5 mg/kg) was administered 5, 10, 15 and 30 min after intraperitoneal injection of graded doses (0.7, 1.25 and 2.5 mg/kg) of SNP. SNP at doses 0.7 and 1.25 mg/kg increased dose dependently the severity of PCT-induced convulsions. But, pretreatment with the higher dose (2.5 mg/kg) of SNP was protective against PCT-induced convulsions. However, post treatment (5 and 10 min) with the same dose exacerbated convulsions and caused death of the animals. These results indicate that the vasodilator effect of SNP and an increased perfusion of PCT into brain may be responsible for the proconvulsant action of SNP. A decreased entry of PCT because of marked vasodilation and hypotension has been speculated for an inhibition of convulsions in animals pretreated with a higher dose of SNP. In conclusion, the results reveal the non-suitability of SNP to be developed as an anticonvulsant.
Rajasekaran
K
K
Department of Pharmacology and Environmental Toxicology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai-600 113.
Reddy
P L
PL
Paul
V
V
D000818:Animals; D003292:Convulsants; D004305:Dose-Response Relationship, Drug; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000627:therapeutic use*; D009599:Nitroprusside / Q000627:therapeutic use*; D010852:Picrotoxin; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D014665:Vasodilator Agents / Q000627:therapeutic use*
D003292:Convulsants; D009569:Nitric Oxide; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D010852:Picrotoxin; D014665:Vasodilator Agents