4-Methylmethcathinone (Mephedrone): Neuropharmacological Effects of a Designer Stimulant of Abuse
4-Methylmethcathinone (Mephedrone): Neuropharmacological Effects of a Designer Stimulant of Abuse
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DOI：
10.1124/jpet.111.184119
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发表时间：
2011-11-01
影响因子：
3.5
通讯作者：
Fleckenstein, Annette E.
中科院分区：
文献类型：
--
作者：
Hadlock, Gregory C.;Webb, Katy M.;Fleckenstein, Annette E.
设计师兴奋剂4-甲基甲卡西酮（甲氧麻黄酮）是最受欢迎的衍生物的自然发生的精神兴奋剂卡西酮。在网上和一些商店里，马诺酮已经可以通过法律的购买，并通过积极的网络营销进行推广。它在包括美国在内的许多国家的滥用是一个严重的公共卫生问题。主要由于最近才出现，没有关于甲氧麻黄酮的正式药效学或药代动力学研究。因此，本研究的目的是评价该药物在大鼠模型中的作用。结果显示，与亚甲二氧基甲基苯丙胺、甲基苯丙胺和甲卡西酮类似，重复甲氧麻黄酮注射（4x 10或25 mg/kg s.c.每次注射，2小时间隔，以经常用于模拟精神兴奋剂“狂欢”治疗的模式施用）引起纹状体多巴胺（DA）和海马5-羟色胺（5-羟色胺; 5 HT）转运蛋白功能的快速降低。吗啡酮还抑制突触体DA和5 HT摄取。像亚甲二氧基甲基苯丙胺，但不像甲基苯丙胺或甲卡西酮，重复甲氧麻黄酮管理也造成持续的多巴胺能，但不是多巴胺能，赤字。然而，甲氧麻黄酮导致DA释放从纹状体悬浮液接近甲基苯丙胺，并自我管理的啮齿动物。开发了一种方法来评估大鼠脑和血浆中的甲氧麻黄酮浓度，并在狂欢治疗后1小时测定甲氧麻黄酮水平。这些数据表明，4-甲基甲卡西酮具有独特的药理学特征，既有滥用倾向，又有神经毒性潜力。
The designer stimulant 4-methylmethcathinone (mephedrone) is among the most popular of the derivatives of the naturally occurring psychostimulant cathinone. Mephedrone has been readily available for legal purchase both online and in some stores and has been promoted by aggressive Web-based marketing. Its abuse in many countries, including the United States, is a serious public health concern. Owing largely to its recent emergence, there are no formal pharmacodynamic or pharmacokinetic studies of mephedrone. Accordingly, the purpose of this study was to evaluate effects of this agent in a rat model. Results revealed that, similar to methylenedioxymethamphetamine, methamphetamine, and methcathinone, repeated mephedrone injections (4x 10 or 25 mg/kg s.c. per injection, 2-h intervals, administered in a pattern used frequently to mimic psychostimulant "binge" treatment) cause a rapid decrease in striatal dopamine (DA) and hippocampal serotonin (5-hydroxy-tryptamine; 5HT) transporter function. Mephedrone also inhibited both synaptosomal DA and 5HT uptake. Like methylenedioxymethamphetamine, but unlike methamphetamine or methcathinone, repeated mephedrone administrations also caused persistent serotonergic, but not dopaminergic, deficits. However, mephedrone caused DA release from a striatal suspension approaching that of methamphetamine and was self-administered by rodents. A method was developed to assess mephedrone concentrations in rat brain and plasma, and mephedrone levels were determined 1 h after a binge treatment. These data demonstrate that mephedrone has a unique pharmacological profile with both abuse liability and neurotoxic potential.