Baumann Michael H, Walters Hailey M, Niello Marco, Sitte Harald H
Designer Drug Research Unit (DDRU) NIDA, IRP, NIH, Baltimore, MD, USA.
Developmental, Cognitive and Behavioral Neuroscience, University of Houston, Houston, TX, USA.
Handb Exp Pharmacol. 2018;252:113-142. doi: 10.1007/164_2018_178.
Synthetic cathinones are derivatives of the naturally occurring compound cathinone, the main psychoactive ingredient in the khat plant Catha edulis. Cathinone is the β-keto analog of amphetamine, and all synthetic cathinones display a β-keto moiety in their structure. Several synthetic cathinones are widely prescribed medications (e.g., bupropion, Wellbutrin), while others are problematic drugs of abuse (e.g., 4-methylmethcathinone, mephedrone). Similar to amphetamines, synthetic cathinones are psychomotor stimulants that exert their effects by impairing the normal function of plasma membrane transporters for dopamine (DAT), norepinephrine (NET), and 5-HT (SERT). Ring-substituted cathinones like mephedrone are transporter substrates that evoke neurotransmitter release by reversing the normal direction of transporter flux (i.e., releasers), whereas pyrrolidine-containing cathinones like 3,4-methylenedioxypyrovalerone (MDPV) are potent transporter inhibitors that block neurotransmitter uptake (i.e., blockers). Regardless of molecular mechanism, all synthetic cathinones increase extracellular monoamine concentrations in the brain, thereby enhancing cell-to-cell monoamine signaling. Here, we briefly review the mechanisms of action, structure-activity relationships, and in vivo pharmacology of synthetic cathinones. Overall, the findings show that certain synthetic cathinones are powerful drugs of abuse that could pose significant risk to users.
合成卡西酮是天然存在的化合物卡西酮的衍生物，卡西酮是巧茶属植物 Catha edulis 中的主要精神活性成分。卡西酮是安非他明的β-酮类似物，所有合成卡西酮在其结构中均显示出β-酮部分。几种合成卡西酮是广泛使用的处方药（例如安非他酮，商品名威博隽），而其他一些则是有问题的滥用药物（例如4-甲基甲卡西酮，甲氧麻黄酮）。与安非他明类似，合成卡西酮是精神运动兴奋剂，它们通过损害多巴胺（DAT）、去甲肾上腺素（NET）和5-羟色胺（SERT）的质膜转运体的正常功能来发挥作用。像甲氧麻黄酮这样的环取代卡西酮是转运体底物，它们通过逆转转运体通量的正常方向来引发神经递质释放（即释放剂），而像3,4-亚甲基二氧吡咯戊酮（MDPV）这样的含吡咯烷卡西酮是有效的转运体抑制剂，可阻断神经递质摄取（即阻断剂）。无论分子机制如何，所有合成卡西酮都会增加大脑细胞外单胺浓度，从而增强细胞间单胺信号传导。在此，我们简要回顾合成卡西酮的作用机制、构效关系和体内药理学。总体而言，研究结果表明某些合成卡西酮是强大的滥用药物，可能对使用者构成重大风险。
