Mayer Felix P, Luf Anton, Nagy Constanze, Holy Marion, Schmid Rainer, Freissmuth Michael, Sitte Harald H
Center of Physiology and Pharmacology, Institute of Pharmacology, Medical University Vienna, Waehringerstrasse 13a, A-1090, Vienna, Austria.
Clinical Department of Laboratory Medicine, Medical University of Vienna, Waehringer Guertel 10-20, 1090, Vienna, Austria.
Curr Top Behav Neurosci. 2017;32:333-350. doi: 10.1007/7854_2016_63.
Psychoactive compounds can cause acute and long-term health problems and lead to addiction. In addition to well-studied and legally controlled compounds like cocaine, new psychoactive substances (NPS) are appearing in street drug markets as replacement strategies and legal alternatives. NPS are effectively marketed as "designer drugs" or "research chemicals" without any knowledge of their underlying pharmacological mode of action and their potential toxicological effects and obviously devoid of any registration process. As of 2016, the knowledge of structure-activity relationships for most NPS is scarce, and predicting detailed pharmacological activity of newly emerging drugs is a challenging task. Therefore, it is important to combine different approaches and employ biological test systems that are superior to mere chemical analysis in recognizing novel and potentially harmful street drugs. In this chapter, we provide a detailed description of techniques to decipher the molecular mechanism of action of NPS that target the high-affinity transporters for dopamine, norepinephrine, and serotonin. In addition, this chapter provides insights into a combined approach to identify and characterize new psychoactive street drugs of unknown content in a collaboration with the Austrian prevention project "checkit!."
精神活性化合物可导致急性和长期健康问题，并引发成瘾。除了像可卡因这样经过充分研究且受到法律管制的化合物外，新型精神活性物质（NPS）正作为替代策略和合法替代品出现在街头毒品市场。NPS被有效地当作“设计药物”或“科研化学品”进行销售，人们对其潜在的药理作用模式和毒理学影响一无所知，而且显然没有任何注册程序。截至2016年，对于大多数NPS的构效关系了解甚少，预测新出现药物的详细药理活性是一项具有挑战性的任务。因此，结合不同方法并采用在识别新型和潜在有害街头毒品方面优于单纯化学分析的生物测试系统非常重要。在本章中，我们详细描述了解密靶向多巴胺、去甲肾上腺素和5-羟色胺高亲和力转运体的NPS作用分子机制的技术。此外，本章还介绍了一种与奥地利预防项目“检查它！”合作，用于识别和表征未知成分新型精神活性街头毒品的综合方法。
