Hasegawa Koutaro, Minakata Kayoko, Suzuki Masako, Suzuki Osamu
Department of Legal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192 Japan.
Forensic Toxicol. 2022;40(2):234-243. doi: 10.1007/s11419-022-00624-y. Epub 2022 Apr 29.
Since the appearance of fentanyl followed by its many kinds of analogues around 1988, North America has been exposed to fierce synthetic opioid pandemic resulting in more than 130,000 deaths due to their overdoses until May 2019, when China declared to prohibit the licit fentanyl analog production. However, the Chinese announcement did not go into force in USA due to the adroit strategies of tough traffickers. Thus, contrary to the expectation, the number of synthetic opioid products and their poisoning cases in USA has increased by about 30%; especially, various benzimidazole synthetic opioids have revived on the illicit drug market during a recent few years. In this article, the recent abrupt changes in the situations of illicit synthetic opioid market and their current abuses are described.
Various databases, such as SciFinder, Google, and Google Scholar, were utilized to collect relevant reports referring old but newly appearing synthetic opioids.
At the present time, there are several families of new synthetic opioids, which are not fentanyl derivatives; MT-45 and its analogs, benzamide and 2-phenylacetamide opioids (U-series opioids), and benzimidazole opioids. Most of the above substances had been developed in 1950s to 1970s, but had never been used as analgesic medicines, because of their severe adverse effects, such as respiratory depression, physical dependence, and resulting deaths. However, there is possibility that these drugs will become main illicit synthetic opioids in place of the fentanyl analogs during coming several years from this time.
All of the above non-fentanyl-derived families had been developed 50-70 years ago to establish them as analgesic medicines, but had been unsuccessful. These drugs largely appeared in the illicit drug markets in North America, Europe, and Australia, during recent years. Pharmacological, toxicological, and metabolic studies are insufficient for benzamide and 2-phenylacetamide opioids, and are very scant especially for benzimidazole opioids. This time we should start studying pharmacotoxicology of the newly emerging synthetic opioids to alert forensic toxicologists in the world and to suppress their rapid and wide spread in the world.
The online version contains supplementary material available at 10.1007/s11419-022-00624-y.
自1988年左右芬太尼及其多种类似物出现以来，北美遭受了激烈的合成阿片类药物大流行，截至2019年5月，因过量服用导致超过13万例死亡，当时中国宣布禁止合法生产芬太尼类似物。然而，由于狡猾的毒贩采取的策略，中国的这一宣布在美国并未生效。因此，与预期相反，美国合成阿片类药物产品及其中毒病例数量增加了约30%；特别是，近年来各种苯并咪唑合成阿片类药物在非法毒品市场上死灰复燃。本文描述了非法合成阿片类药物市场形势最近的突然变化及其当前的滥用情况。
利用各种数据库，如SciFinder、谷歌和谷歌学术，收集有关旧的但新出现的合成阿片类药物的相关报告。
目前，有几类新的合成阿片类药物，它们不是芬太尼衍生物；MT-45及其类似物、苯甲酰胺和2-苯乙酰胺类阿片（U系列阿片）以及苯并咪唑类阿片。上述大多数物质在20世纪50年代至70年代开发，但由于其严重的不良反应，如呼吸抑制、身体依赖和导致死亡，从未被用作镇痛药。然而，从现在起的几年内，这些药物有可能取代芬太尼类似物成为主要的非法合成阿片类药物。
上述所有非芬太尼衍生的类别在50 - 70年前开发出来是为了将它们用作镇痛药，但均未成功。近年来，这些药物大量出现在北美、欧洲和澳大利亚的非法毒品市场。对苯甲酰胺和2-苯乙酰胺类阿片的药理、毒理和代谢研究不足，尤其是对苯并咪唑类阿片的研究非常匮乏。这次我们应该开始研究新出现的合成阿片类药物的药物毒理学，以警示全球的法医毒理学家，并抑制它们在全球的迅速广泛传播。
在线版本包含可在10.1007/s11419-022-00624-y获取的补充材料。
