去甲肾上腺素能系统对埃必定镇痛作用的影响

在大鼠电刺激甩尾测痛模型上,sc或icv埃必定(ipalbidine,Ipa)均具有剂量依赖性的镇痛作用,而脊髓蛛网膜下腔注射Ipa人产生镇痛作用;预先给予利血平可以取消scIpa的镇痛作用,这一作用可被icv补充NE所翻转;电解损毁大鼠叹侧蓝斑,ip二乙基二硫代氨基甲酸钠200mg·kg^-1,酚妥拉明ip10mg·kg^-1或icv150μg和sc哌唑嗪5mg·kg^-1均能使Ipa的镇痛作用明显减弱或消失,而sc育亨宾5mg·kg^-1和ip普萘洛尔10mg·kg^-1对Ipa的镇痛作用无明显影响。上述结果提示Ipa在中枢有镇痛作用,其部位主要在脊髓以上的神经结构,Ipa的镇痛作用可能与去甲肾上腺素能系统的a₁受体有关,而与a₂和β受体无明显关系。

EFFECT OF NOREPINEPHRINEKGIC SYSTEM ON IPALBIDINE ANALGESIA

Ipalbidine(Ipa)is a photoactive alkaloid isolated from the seeds of ipomoea hardwickki Hemsl.The analgesic effects of Ipa were determined by rat tail flick method.A dose-dependent analgesic effect was found after sc or icv administration of Ipa,but no analgesia wasobserved after intrathecal injection,indicating that the analgesic effect of Ipa is central in origin,and itacts mainly on supraspinal substrate.The analgesic effect induced by Ipa(60 mg·kg^-1,sc)was markedly reduced by reserpine(2mg·kg^-1,ip)given 24 h before Ipa, which was reversed by combined administration with icvnorepinephrine(NE).In addition, Ipa-induced analgesia was significantly attenuated by electrolyticlesion of bilateral destruction of locus coeruleus.and combined administration withdiethyldithiocarbamate(200 mg·kg^-1,ip),phentolamine(10 mg·kg^-1,ip or icv),and prazosin(3mg·kg^-1,sc).But no influence was observed on the analgesia of Ipa after administration ofyohimbine(5 mg·kg^-1,sc) or propranolol(10 mg·kg^-1,ip).These results suggest that the analgesiacaused by Ipa is closely related to the function of the central norepinephrinergic system,and probablymediated by indirectly acting on α₁ receptors,but not α₂ orβreceptors.