Moosmann Bjoern, Auwärter Volker
Institute of Forensic Medicine, Forensic Toxicology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
Institute of Forensic Medicine, Forensic Toxicology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Handb Exp Pharmacol. 2018;252:383-410. doi: 10.1007/164_2018_154.
Benzodiazepines have been introduced as medical drugs in the 1960s. They replaced the more toxic barbiturates, which were commonly used for treatment of anxiety or sleep disorders at the time. However, benzodiazepines show a high potential of misuse and dependence. Although being of great value as medicines, dependence to these drugs is a concern worldwide, in part due to overprescription and easy availability. Therefore, the phenomenon of benzodiazepines sold via Internet shops without restrictions at low prices is alarming and poses a serious threat to public health. Most of these compounds (with the exception of, e.g., phenazepam and etizolam) have never been licensed as medical drugs in any part of the world and are structurally derived from medically used benzodiazepines. Strategies of clandestine producers to generate new compounds include typical structural variations of medically used 1,4-benzodiazepines based on structure-activity relationships as well as synthesis of active metabolites and triazolo analogs of these compounds. As they were obviously designed to circumvent national narcotics laws or international control, they can be referred to as "designer benzodiazepines." The majority of these compounds, such as diclazepam, clonazolam, and nitrazolam, have been described in scientific or patent literature. However, little is known about their pharmacological properties and specific risks related to their use. This chapter describes the phenomenon of designer benzodiazepines and summarizes the available data on pharmacokinetics and pharmacodynamics as well as analytical approaches for their detection.
苯二氮䓬类药物于20世纪60年代作为医疗药物被引入。它们取代了当时常用于治疗焦虑或睡眠障碍的毒性更强的巴比妥类药物。然而,苯二氮䓬类药物显示出很高的滥用和依赖潜力。尽管作为药物具有很大价值,但对这些药物的依赖在全球范围内都是一个令人担忧的问题,部分原因是过度处方和容易获得。因此,通过网上商店无限制低价销售苯二氮䓬类药物的现象令人震惊,并对公众健康构成严重威胁。这些化合物中的大多数(例如,除了芬那西泮和依替唑仑)在世界任何地区都从未被批准为医疗药物,并且在结构上源自医用苯二氮䓬类药物。秘密生产者制造新化合物的策略包括基于构效关系对医用1,4 - 苯二氮䓬类药物进行典型的结构变异,以及合成这些化合物的活性代谢物和三唑类似物。由于它们显然是为了规避国家麻醉药品法律或国际管制而设计的,因此可以被称为“设计型苯二氮䓬类药物”。这些化合物中的大多数,如地西泮、氯硝西泮和硝西泮,已在科学或专利文献中有所描述。然而,关于它们的药理特性以及与使用相关的特定风险却知之甚少。本章描述了设计型苯二氮䓬类药物的现象,并总结了关于其药代动力学和药效学的现有数据以及它们的检测分析方法。