Reis G M L, Doretto M C, Duarte I D G, Tatsuo M A K F
Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
Braz J Med Biol Res. 2003 Sep;36(9):1263-8. doi: 10.1590/s0100-879x2003000900018. Epub 2003 Aug 19.
It was previously reported that systemic administration of dipyrone inhibited the tonic component of generalized tonic-clonic seizures in both the electroshock and the audiogenic seizure models. The aim of the present study was to investigate the mechanisms involved in the anticonvulsant action of dipyrone by assessing the role of nitric oxide and opioids in the electroshock (female 60- to 90-day-old Wistar rats, N = 5-11) and audiogenic seizure (female 60- to 90-day-old Wistar audiogenic rats, N = 5-11) models of epilepsy. Naloxone (5 mg/kg, sc) significantly reversed the anticonvulsant effect of dipyrone in rats submitted to the induction of audiogenic seizures (ANOVA/Bonferroni's test), suggesting the involvement of opioid peptides in this action. In the electroshock model no reversal of the anticonvulsant effect of dipyrone by naloxone (5 mg/kg, sc) was demonstrable. The acute (120 mg/kg, ip) and chronic (25 mg/kg, ip, twice a day/4 days) administration of L-NOARG did not reverse the anticonvulsant action of dipyrone in the audiogenic seizure model, suggesting that the nitric oxide pathway does not participate in such effect. Indomethacin (10, 20 and 30 mg/kg, ip) used for comparison had no anticonvulsant effect in the audiogenic seizure model. In conclusion, opioid peptides but not nitric oxide seem to be involved in the anticonvulsant action of dipyrone in audiogenic seizures.
先前有报道称，在电休克和听源性癫痫发作模型中，全身性给予安乃近可抑制全身性强直 - 阵挛性癫痫发作的强直成分。本研究的目的是通过评估一氧化氮和阿片类物质在癫痫的电休克模型（60至90日龄雌性Wistar大鼠，N = 5 - 11）和听源性癫痫发作模型（60至90日龄雌性Wistar听源性大鼠，N = 5 - 11）中的作用，来研究安乃近抗惊厥作用的机制。纳洛酮（5 mg/kg，皮下注射）可显著逆转安乃近对听源性癫痫发作诱导大鼠的抗惊厥作用（方差分析/邦费罗尼检验），提示阿片肽参与了这一作用。在电休克模型中，纳洛酮（5 mg/kg，皮下注射）未能证明可逆转安乃近的抗惊厥作用。L - NOARG的急性（120 mg/kg，腹腔注射）和慢性（25 mg/kg，腹腔注射，每天两次/共4天）给药在听源性癫痫发作模型中均未逆转安乃近的抗惊厥作用，提示一氧化氮途径不参与此效应。用于比较的吲哚美辛（10、20和30 mg/kg，腹腔注射）在听源性癫痫发作模型中无抗惊厥作用。总之，阿片肽而非一氧化氮似乎参与了安乃近在听源性癫痫发作中的抗惊厥作用。
