• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验

以U-47700为例,采用体外和体内方法进行法医毒理学应用,对合成阿片类药物进行代谢评估。

Metabolic Evaluation of Synthetic Opioids on the Example of U-47700 with the Use of In Vitro and In Vivo Methods for Forensic Toxicology Application.

作者信息

Rojek Sebastian, Poljańska Ewa, Chaim Weronika, Maciów-Głąb Martyna, Bystrowska Beata

机构信息

Department of Forensic Medicine, Faculty of Medicine, Jagiellonian University Medical College, Grzegórzecka 16 Str., 31-531 Kraków, Poland.

Toxicology Research Group, Department of Toxicology, Jagiellonian University Medical College, Medyczna 9 Str., 30-688 Krakow, Poland.

出版信息

Toxics. 2023 Feb 25;11(3):220. doi: 10.3390/toxics11030220.

DOI:10.3390/toxics11030220
PMID:36976985
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10053220/
Abstract

Legal highs present a great threat to health, especially in groups of people experimenting with psychoactive substances. The lack of available knowledge on the biotransformation of these substances necessitates symptomatic treatment in the event of intoxication, which, unfortunately, may be ineffective. Opioids, including heroin analogues, such as U-47700, constitute a special group of designer drugs. In this study, a multi-directional approach to trace the biotransformation of U-47700 in living organisms was used. For this purpose, the in silico assessment (ADMET Predictor) was used first and then followed by an in vitro study using human liver microsomes and the S9 fraction. The biotransformation was then followed in an animal model (Wistar rats). Tissues such as blood, brain and liver were collected for analysis. The study was performed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). The obtained results were compared to those obtained from the analysis of autopsy materials (cases analysed in the Toxicology Laboratory of the Department of Forensic Medicine, Jagiellonian University Medical College in Krakow).

摘要

新型毒品对健康构成巨大威胁,尤其是在尝试使用精神活性物质的人群中。由于缺乏关于这些物质生物转化的现有知识,中毒时需要进行对症治疗,但不幸的是,这种治疗可能无效。阿片类药物,包括海洛因类似物,如U-47700,构成了一类特殊的合成毒品。在本研究中,采用了多方向方法来追踪U-47700在生物体内的生物转化。为此,首先使用计算机模拟评估(ADMET Predictor),然后进行使用人肝微粒体和S9组分的体外研究。随后在动物模型(Wistar大鼠)中追踪生物转化过程。收集血液、大脑和肝脏等组织进行分析。该研究使用液相色谱-串联质谱法(LC-MS/MS)进行。将获得的结果与从尸检材料分析中获得的结果进行比较(这些病例在克拉科夫雅盖隆大学医学院法医学系毒理学实验室进行分析)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0c2/10053220/5571fadc1e5b/toxics-11-00220-g003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0c2/10053220/a01c41c3cac6/toxics-11-00220-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0c2/10053220/7ddb9ef2cffe/toxics-11-00220-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0c2/10053220/5571fadc1e5b/toxics-11-00220-g003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0c2/10053220/a01c41c3cac6/toxics-11-00220-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0c2/10053220/7ddb9ef2cffe/toxics-11-00220-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0c2/10053220/5571fadc1e5b/toxics-11-00220-g003a.jpg

相似文献

1
Metabolic Evaluation of Synthetic Opioids on the Example of U-47700 with the Use of In Vitro and In Vivo Methods for Forensic Toxicology Application.以U-47700为例,采用体外和体内方法进行法医毒理学应用,对合成阿片类药物进行代谢评估。
Toxics. 2023 Feb 25;11(3):220. doi: 10.3390/toxics11030220.
2
Brorphine-Investigation and quantitation of a new potent synthetic opioid in forensic toxicology casework using liquid chromatography-mass spectrometry.布若啡-液相色谱-质谱法在法医毒物学中的调查和定量检测一种新型强力合成阿片类药物。
J Forensic Sci. 2021 Mar;66(2):664-676. doi: 10.1111/1556-4029.14623. Epub 2020 Nov 17.
3
Suspect and non-target screening workflows to investigate the in vitro and in vivo metabolism of the synthetic cannabinoid 5Cl-THJ-018.疑似物和非靶标筛查工作流程,以研究合成大麻素 5Cl-THJ-018 的体外和体内代谢情况。
Drug Test Anal. 2019 Mar;11(3):479-491. doi: 10.1002/dta.2508. Epub 2018 Oct 23.
4
Characterization and in vitro phase I microsomal metabolism of designer benzodiazepines: An update comprising flunitrazolam, norflurazepam, and 4'-chlorodiazepam (Ro5-4864).设计苯二氮䓬类药物的特征描述和体外 I 相微粒体代谢:包括氟硝西泮、去甲氟安定和 4'-氯二氮䓬(Ro5-4864)的更新。
Drug Test Anal. 2019 Mar;11(3):541-549. doi: 10.1002/dta.2561. Epub 2019 Feb 5.
5
Toxicokinetics and analytical toxicology of the abused opioid U-48800 - in vitro metabolism, metabolic stability, isozyme mapping, and plasma protein binding.滥用阿片类药物 U-48800 的毒代动力学和分析毒理学-体外代谢、代谢稳定性、同工酶图谱和血浆蛋白结合。
Drug Test Anal. 2019 Oct;11(10):1572-1580. doi: 10.1002/dta.2683. Epub 2019 Sep 10.
6
Analysis of U-47700, a Novel Synthetic Opioid, in Human Urine by LC-MS-MS and LC-QToF.采用液相色谱-串联质谱法和液相色谱-四极杆飞行时间质谱法对新型合成阿片类物质U-47700进行人尿分析。
J Anal Toxicol. 2017 Apr 1;41(3):173-180. doi: 10.1093/jat/bkw131.
7
Diphenidine, a new psychoactive substance: metabolic fate elucidated with rat urine and human liver preparations and detectability in urine using GC-MS, LC-MS , and LC-HR-MS.二苯乙胺,一种新型精神活性物质:通过大鼠尿液和人肝脏制剂阐明其代谢命运,并利用气相色谱 - 质谱联用仪(GC-MS)、液相色谱 - 质谱联用仪(LC-MS)和液相色谱 - 高分辨质谱仪(LC-HR-MS)检测尿液中的该物质。
Drug Test Anal. 2016 Oct;8(10):1005-1014. doi: 10.1002/dta.1946. Epub 2016 Jan 26.
8
Phenethylamine-derived new psychoactive substances 2C-E-FLY, 2C-EF-FLY, and 2C-T-7-FLY: Investigations on their metabolic fate including isoenzyme activities and their toxicological detectability in urine screenings.苯乙胺类新型精神活性物质 2C-E-FLY、2C-EF-FLY 和 2C-T-7-FLY:代谢途径研究,包括同工酶活性及尿液筛查中的毒理学检测。
Drug Test Anal. 2019 Oct;11(10):1507-1521. doi: 10.1002/dta.2675. Epub 2019 Jul 31.
9
Fentanyl, fentanyl analogs and novel synthetic opioids: A comprehensive review.芬太尼、芬太尼类似物和新型合成阿片类药物:全面综述。
Neuropharmacology. 2018 May 15;134(Pt A):121-132. doi: 10.1016/j.neuropharm.2017.10.016. Epub 2017 Oct 14.
10
Biotransformation and detectability of the new psychoactive substances N,N-diallyltryptamine (DALT) derivatives 5-fluoro-DALT, 7-methyl-DALT, and 5,6-methylenedioxy-DALT in urine using GC-MS, LC-MS, and LC-HR-MS/MS.使用气相色谱-质谱联用仪(GC-MS)、液相色谱-质谱联用仪(LC-MS)和液相色谱-高分辨质谱联用仪/质谱(LC-HR-MS/MS)对新型精神活性物质N,N-二烯丙基色胺(DALT)衍生物5-氟-DALT、7-甲基-DALT和5,6-亚甲基二氧基-DALT在尿液中的生物转化及可检测性进行研究。
Anal Bioanal Chem. 2017 Feb;409(6):1681-1695. doi: 10.1007/s00216-016-0117-5. Epub 2016 Dec 8.

引用本文的文献

1
In silico and in vitro metabolism studies of the new synthetic opiate AP-237 (bucinnazine) using bioinformatics tools.使用生物信息学工具对新型合成阿片类药物 AP-237(布西嗪)进行体内和体外代谢研究。
Arch Toxicol. 2024 Jan;98(1):165-179. doi: 10.1007/s00204-023-03617-x. Epub 2023 Oct 15.

本文引用的文献

1
Reports of Adverse Events Associated with Use of Novel Psychoactive Substances, 2017-2020: A Review.报告称,2017 年至 2020 年与新型精神活性物质使用相关的不良事件:一项综述。
J Anal Toxicol. 2022 Jul 14;46(6):e116-e185. doi: 10.1093/jat/bkac023.
2
Are the N-demethylated metabolites of U-47700 more active than their parent compound? In vitro μ-opioid receptor activation of N-desmethyl-U-47700 and N,N-bisdesmethyl-U-47700.U-47700 的 N-去甲基代谢产物是否比其母体化合物更活跃?N-去甲基-U-47700 和 N,N-双去甲基-U-47700 的体外 μ-阿片受体激活作用。
Drug Test Anal. 2022 Apr;14(4):713-717. doi: 10.1002/dta.3182. Epub 2021 Oct 25.
3
Toxicokinetics of U-47700, tramadol, and their main metabolites in pigs following intravenous administration: is a multiple species allometric scaling approach useful for the extrapolation of toxicokinetic parameters to humans?
U-47700、曲马多及其静脉给药后主要代谢物在猪体内的毒代动力学:多物种外推比例法是否可用于将毒代动力学参数外推至人体?
Arch Toxicol. 2021 Dec;95(12):3681-3693. doi: 10.1007/s00204-021-03169-y. Epub 2021 Oct 3.
4
Perimortem Distribution of U-47700, Tramadol and Their Main Metabolites in Pigs Following Intravenous Administration.静脉注射 U-47700、曲马多及其主要代谢物在猪体内的死后分布。
J Anal Toxicol. 2022 May 20;46(5):479-486. doi: 10.1093/jat/bkab044.
5
Psychopharmacological characterization of an emerging drug of abuse, a synthetic opioid U-47700, in adult zebrafish.新兴滥用药物——合成阿片类药物 U-47700 在成年斑马鱼体内的精神药理学特征。
Brain Res Bull. 2021 Feb;167:48-55. doi: 10.1016/j.brainresbull.2020.11.017. Epub 2020 Nov 26.
6
U-47700 and Its Analogs: Non-Fentanyl Synthetic Opioids Impacting the Recreational Drug Market.U-47700及其类似物:影响娱乐性毒品市场的非芬太尼类合成阿片类药物
Brain Sci. 2020 Nov 23;10(11):895. doi: 10.3390/brainsci10110895.
7
Heroin-Related Compounds and Metabolic Ratios in Postmortem Samples Using LC-MS-MS.使用 LC-MS-MS 分析死后样本中的海洛因相关化合物和代谢比。
J Anal Toxicol. 2021 Mar 12;45(3):215-225. doi: 10.1093/jat/bkaa157.
8
Pharmacodynamics and pharmacokinetics of the novel synthetic opioid, U-47700, in male rats.新型合成阿片类药物 U-47700 在雄性大鼠中的药效学和药代动力学。
Neuropharmacology. 2020 Oct 15;177:108195. doi: 10.1016/j.neuropharm.2020.108195. Epub 2020 Jun 10.
9
Are pigs a suitable animal model for in vivo metabolism studies of new psychoactive substances? A comparison study using different in vitro/in vivo tools and U-47700 as model drug.猪是否适合作为新型精神活性物质体内代谢研究的动物模型?使用不同的体外/体内工具和 U-47700 作为模型药物进行的比较研究。
Toxicol Lett. 2020 Sep 1;329:12-19. doi: 10.1016/j.toxlet.2020.04.001. Epub 2020 May 4.
10
Prodrugs of New Psychoactive Substances (NPS): A New Challenge.新精神活性物质(NPS)前药:新的挑战。
J Forensic Sci. 2020 May;65(3):913-920. doi: 10.1111/1556-4029.14268. Epub 2020 Jan 13.