对 MDMA（“摇头丸”）拮抗剂纳曲胺的合成研究和药理学评价。
Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine.
机构信息
Department of Chemistry, Hunter College and the Graduate Center of the City University of New York, 695 Park Avenue, New York, NY 10065, USA.
出版信息
Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31. doi: 10.1016/j.bmcl.2009.11.053. Epub 2009 Nov 20.
Abstract
The naturally occurring aporphine alkaloid nantenine, has been shown to antagonize behavioral and physiological effects of MDMA in mice. We have synthesized (+/-)-nantenine via an oxidative cyclization reaction with PIFA and evaluated its binding profile against a panel of CNS targets. To begin to understand the importance of the chiral center of nantenine with regards to its capacity to antagonize the effects of MDMA in vivo, (R)- and (S)-nantenine were prepared and evaluated in a food-reinforced operant task in rats. Pretreatment with either nantenine enantiomer (0.3mg/kg ip) completely blocked the behavioral suppression induced upon administration of 3.0mg/kg MDMA. (+/-)-Nantenine displayed high affinity and selectivity for the alpha(1A) adrenergic receptor among several other receptors suggesting that this alpha(1) subtype may be significantly involved in the anti-MDMA effects of the enantiomers.
摘要
天然阿朴啡类生物碱纳曲酮已被证明能拮抗 MDMA 在小鼠体内的行为和生理效应。我们通过与 PIFA 的氧化环化反应合成了（±）-纳曲酮，并评估了其针对一组中枢神经系统靶标的结合特性。为了开始了解纳曲酮手性中心对于其拮抗 MDMA 体内效应的重要性，我们制备了（R）-和（S）-纳曲酮，并在大鼠食物强化操作性任务中进行了评估。纳曲酮对映异构体（0.3mg/kg ip）预处理完全阻断了 3.0mg/kg MDMA 给药引起的行为抑制。（±）-纳曲酮对几种其他受体中的α1A 肾上腺素能受体显示出高亲和力和选择性，这表明这种α1 亚型可能与对映异构体的抗 MDMA 效应有显著关系。
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