Synthetic opioids constitute one of the fastest-growing groups of new psychoactive substances (NPS) worldwide. With fentanyl analogues being increasingly controlled via classwide scheduling, many non-fentanyl-related opioids are now emerging on the recreational opioid market, rendering the landscape highly complex and dynamic. While new compounds are entering the supply in rapid and unpredictable manners, some recent patterns have become apparent. Many of these newly emerging opioids are being pirated from early patent literature and/or research papers, synthesized and sold online through various channels. Burdened by the identification of every newly emerging drug, many toxicology labs struggle to keep up. Moreover, by the time a ‘new’ drug is controlled via legislative measures, illicit drug markets will have already adapted and diversified as manufacturers work to avoid the restricted product(s). Hence, the typical life cycle of an NPS opioid is generally short (less than 6 months to 1 year), with only a few drugs escalating to significant numbers of detections. In this review, we summarize the key events in the emergence, rise and subsequent decline of two non-fentanyl opioids—isotonitazene and brorphine. These two opioids sequentially dominated the NPS opioid market in 2019 and 2020. Both isotonitazene and brorphine remained in circulation for over a year, each contributing to hundreds of deaths and adverse events. By detailing the life cycles of these opioids from their earliest synthesis as described in scientific literature to their subsequent rise and fall on recreational markets, this review illustrates the new characteristic life cycle of synthetic opioids in the ‘post-fentanyl-analogue’ era.

中文翻译：

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异渗氮酮和溴吗啡的兴衰：合成阿片类药物领域的两颗新星


合成阿片类药物是全球增长最快的新型精神活性物质 (NPS) 之一。随着芬太尼类似物越来越多地通过全班调度进行控制，许多非芬太尼相关的阿片类药物现在出现在娱乐性阿片类药物市场上，使市场格局变得高度复杂和动态。虽然新化合物正在以快速且不可预测的方式进入供应，但最近的一些模式已经变得明显。许多新兴的阿片类药物是从早期专利文献和/或研究论文中盗版的，通过各种渠道合成并在线销售。背负着识别每一种新出现的药物的重担，许多毒理学实验室都在努力跟上。此外，当“新”药物通过立法措施受到控制时，随着制造商努力避免使用受限制的产品，非法药物市场将已经适应并多样化。因此，NPS 阿片类药物的典型生命周期通常很短（不到 6 个月到 1 年），只有少数药物升级到大量检测。在这篇综述中，我们总结了两种非芬太尼阿片类药物——异托尼嗪和溴啡的出现、上升和随后下降的关键事件。这两种阿片类药物在 2019 年和 2020 年连续主导了 NPS 阿片类药物市场。异渗氮酮和溴啡均已流通了一年多，分别导致数百人死亡和不良事件。通过详细介绍这些阿片类药物从科学文献中描述的最早合成到随后在娱乐市场上的兴衰的生命周期，本综述阐明了“后芬太尼类似物”时代合成阿片类药物新的特征生命周期。