Simmler Linda D, Liechti Matthias E
Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland.
Division of Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland.
Handb Exp Pharmacol. 2018;252:143-164. doi: 10.1007/164_2018_113.
New psychoactive substances (NPS) with amphetamine-, aminoindan-, and benzofuran basic chemical structures have recently emerged for recreational drug use. Detailed information about their psychotropic effects and health risks is often limited. At the same time, it emerged that the pharmacological profiles of these NPS resemble those of amphetamine or 3,4-methylenedioxymethamphetamine (MDMA). Amphetamine-like NPS induce psychostimulation and euphoria mediated predominantly by norepinephrine (NE) and dopamine (DA) transporter (NET and DAT) inhibition and transporter-mediated release of NE and DA, thus showing a more catecholamine-selective profile. MDMA-like NPS frequently induce well-being, empathy, and prosocial effects and have only moderate psychostimulant properties. These MDMA-like substances primarily act by inhibiting the serotonin (5-HT) transporter (SERT) and NET, also inducing 5-HT and NE release. Monoamine receptor interactions vary considerably among amphetamine- and MDMA-like NPS. Clinically, amphetamine- and MDMA-like NPS can induce sympathomimetic toxicity. The aim of this chapter is to review the state of knowledge regarding these substances with a focus on the description of the in vitro pharmacology of selected amphetamine- and MDMA-like NPS. In addition, it is aimed to provide links between pharmacological profiles and in vivo effects and toxicity, which leads to the conclusion that abuse liability for amphetamine-like NPS may be higher than for MDMA-like NPS, but that the risk for developing the life-threatening serotonin syndrome may be increased for MDMA-like NPS.
最近出现了具有苯丙胺、氨基茚和苯并呋喃基本化学结构的新型精神活性物质（NPS）用于娱乐性药物使用。关于它们的精神作用和健康风险的详细信息往往有限。与此同时，发现这些NPS的药理学特征类似于苯丙胺或3,4-亚甲基二氧基甲基苯丙胺（摇头丸）。类似苯丙胺的NPS主要通过抑制去甲肾上腺素（NE）和多巴胺（DA）转运体（NET和DAT）以及转运体介导的NE和DA释放来诱导精神兴奋和欣快感，因此显示出更具儿茶酚胺选择性的特征。类似摇头丸的NPS经常诱导幸福感、同理心和亲社会效应，并且只有适度的精神兴奋特性。这些类似摇头丸的物质主要通过抑制5-羟色胺（5-HT）转运体（SERT）和NET起作用，也诱导5-HT和NE释放。在类似苯丙胺和类似摇头丸的NPS中，单胺受体相互作用差异很大。临床上，类似苯丙胺和类似摇头丸的NPS可诱发拟交感神经毒性。本章的目的是回顾关于这些物质的知识状况，重点描述选定的类似苯丙胺和类似摇头丸的NPS的体外药理学。此外，旨在提供药理学特征与体内效应和毒性之间的联系，从而得出结论：类似苯丙胺的NPS的滥用可能性可能高于类似摇头丸的NPS，但类似摇头丸的NPS发生危及生命的5-羟色胺综合征的风险可能会增加。
