Rajasekaran K, Reddy P L, Paul V
Department of Pharmacology and Environmental Toxicology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai-600 113.
Indian J Physiol Pharmacol. 2001 Jan;45(1):95-100.
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.
一氧化氮（NO）作为一种气态神经递质，据报道具有内源性抗惊厥特性。这促使人们提出开发NO供体作为抗惊厥药物的建议。在本研究中，研究了NO供体硝普钠（SNP）对印防己毒素（PCT）诱导惊厥的影响。在腹腔注射分级剂量（0.7、1.25和2.5mg/kg）的SNP后5、10、15和30分钟，给予惊厥剂量的PCT（5mg/kg）。0.7和1.25mg/kg剂量的SNP剂量依赖性地增加了PCT诱导惊厥的严重程度。但是，用较高剂量（2.5mg/kg）的SNP预处理可预防PCT诱导的惊厥。然而，用相同剂量进行后处理（5和10分钟）会加剧惊厥并导致动物死亡。这些结果表明，SNP的血管舒张作用以及PCT向脑内灌注增加可能是SNP促惊厥作用的原因。有人推测，由于明显的血管舒张和低血压导致PCT进入减少，从而抑制了用较高剂量SNP预处理动物的惊厥发作。总之，结果表明SNP不适合开发为抗惊厥药物。
