Pharmacological profile of mephedrone analogs and related new psychoactive substances
Pharmacological profile of mephedrone analogs and related new psychoactive substances
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DOI：
10.1016/j.neuropharm.2017.07.026
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发表时间：
2018-05-15
影响因子：
4.7
通讯作者：
Liechti, Matthias E.
中科院分区：
文献类型：
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作者：
Luethi, Dino;Kolaczynska, Karolina E.;Liechti, Matthias E.
背景：甲氧麻黄酮是一种人工合成的卡西酮，是目前最常用的新型精神活性物质之一。本研究的目的是表征新型甲氧麻黄酮类似物和相关新出现的设计兴奋剂的体外药理学。方法：测定转运体转染的人胚胎肾293细胞中去甲肾上腺素、多巴胺和血清素转运体的抑制作用和单胺释放。我们还评估了单胺受体和转运体的结合亲和力。结果：甲氧麻黄酮类似物能有效抑制去甲肾上腺素转运体，除3-甲基甲卡西酮（3-MMC）外，对血清素转运体的抑制作用强于多巴胺转运体。与经典的安非他明类似，甲氧麻黄酮类似物是底物型单胺释放剂。5-（2-氨基丙基）吲哚（5- it）是一种高效的单胺转运蛋白抑制剂和多巴胺和血清素的释放剂。与安非他明不同，4-甲基安非他明（4-MA）介导所有三种单胺的外排，并且比多巴胺转运体更有效地抑制血清素转运体。n -甲基-2-氨基茚（n -甲基-2- ai）是一种选择性去甲肾上腺素转运体抑制剂和去甲肾上腺素释放剂，而5-甲氧基-6-甲基-2-氨基茚（MMAI）是一种选择性血清素转运体抑制剂和血清素释放剂。所有的药物都与单胺受体相互作用。结论：二甲基甲卡西酮、4-MA和MMAI对血清素和多巴胺转运体的主要作用表明，二甲基甲西酮、4-MA和MMAI具有类似3,4-亚甲基二氧基甲基苯丙胺的致动作用，而3- mmc、5-IT和n -甲基-2- ai具有类似安非他明的兴奋剂性质。由于与甲氧麻黄酮的药理和结构相似，这些类似物也有类似的健康风险。这篇文章是题为“设计毒品和合法兴奋剂”特刊的一部分。
Background: Mephedrone is a synthetic cathinone and one of the most popular recreationally used new psychoactive substances. The aim of the present study was to characterize the in vitro pharmacology of novel analogs of mephedrone and related newly emerged designer stimulants. Methods: We determined norepinephrine, dopamine, and serotonin transporter inhibition potencies and monoamine release in transporter-transfected human embryonic kidney 293 cells. We also assessed monoamine receptor and transporter binding affinities.Results: Mephedrone analogs potently inhibited the norepinephrine transporter and, with the exception of 3-methylmethcathinone (3-MMC), inhibited the serotonin transporter more potently than the dopamine transporter. Similar to classic amphetamines, mephedrone analogs were substrate-type monoamine releasers. 5-(2-Aminopropyl)indole (5-IT) was a highly potent monoamine transporter inhibitor and a releaser of dopamine and serotonin. 4-Methylamphetamine (4-MA) mediated efflux of all three monoamines and inhibited the serotonin transporter more potently than the dopamine transporter, unlike amphetamine. N-methyl-2-amminoindane (N-methyl-2-AI) was a selective norepinephrine transporter inhibitor and norepinephrine releaser, whereas 5-methoxy-6-methyl-2-aminoindane (MMAI) was a selective serotonin transporter inhibitor and serotonin releaser. All of the drugs interacted with monoamine receptors.Conclusion: The predominant actions on serotonin vs dopamine transporters suggest that dimethylmethcathinones, 4-MA, and MMAI cause entactogenic effects similar to 3,4-methylenedioxymethamphetamine, whereas 3-MMC, 5-IT, and N-methyl-2-AI have more stimulant-type properties like amphetamine. Because of pharmacological and structural similarity to mephedrone, similar health risks can be expected for these analogs. This article is part of the Special Issue entitled 'Designer Drugs and Legal Highs.'