Antinociceptive properties of neurosteroids III: experiments with alphadolone given intravenously, intraperitoneally, and intragastrically.
Antinociceptive properties of neurosteroids III: experiments with alphadolone given intravenously, intraperitoneally, and intragastrically.
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DOI：
10.1093/bja/86.5.704
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发表时间：
2001-05
影响因子：
9.8
通讯作者：
R. Nadeson;Colin S. Goodchild
中科院分区：
文献类型：
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作者：
R. Nadeson;Colin S. Goodchild
兽用神经类固醇麻醉剂Saffan具有与现在从人类使用中撤回的Althesin相同的配方，并且是两种神经类固醇，阿法沙龙和阿法沙龙的混合物。据报道，这两种孕烷的分子结构及其作为静脉注射麻醉剂的性质相似。初步实验表明，当腹膜内给药时，曲马多龙引起强大的抗伤害感受作用而没有镇静作用。在该研究中，将曲马多龙静脉内给药于大鼠（体重100-200 g），腹腔注射，和胃内注射。静脉注射曲马多龙（25 mg/kg）可引起麻醉和镇静作用，而腹腔注射（0.1-100 mg/kg）和灌胃给药（750 mg/kg）则无此作用。在没有镇静作用的情况下，胃内给予曲马多龙可产生抗伤害效应，通过电流阈值试验进行评估（反应2.2 x给药前对照值）。鞘内注射荷包牡丹碱（10 pmol）可逆转脊髓水平的这些效应。我们的结论是，在肝脏中产生的醋酸泼尼松龙的代谢产物导致在腹膜内和胃内给予母体化合物后的抗伤害作用。这种抗伤害感受涉及脊髓GABA（A）受体，即使药物是通过非脊髓途径给药。
The veterinary neurosteroid anaesthetic Saffan has the same formulation as Althesin now withdrawn from human use and is a mixture of two neurosteroids, alphadolone, and alphaxalone. The molecular structures of these two pregnanes and their properties as i.v. anaesthetics were reported to be similar. Preliminary experiments showed that alphadolone caused powerful antinociceptive effects without sedation when given i.p. In this study, alphadolone was given to rats (weight 100-200 g) i.v., i.p., and intragastrically. I.v. injections of alphadolone (25 mg kg(-1)) caused anaesthesia and sedation, whereas i.p. (0.1-100 mg kg(-1)) and intragastric administration (750 mg kg(-1)) produced no such effects. Intragastric alphadolone caused antinociceptive effects assessed with the electrical current threshold test (response 2.2 x pre-drug control values) without sedation. These effects were reversed at the level of the spinal cord by intrathecally-administered bicuculline (10 pmol). We conclude that a metabolite of alphadolone acetate produced in the liver leads to antinociceptive effects after i.p. and intragastric administration of the parent compound. This antinociception involves spinal cord GABA(A) receptors, even though the drug was administered via a non-spinal route.