Report on a novel emerging class of highly potent benzimidazole NPS opioids: Chemical and in vitro functional characterization of isotonitazene

Drug Testing and Analysis - Tập 12 Số 4 - Trang 422-430 - 2020
Peter Blanckaert1, Annelies Cannaert2, Katleen Van Uytfanghe2, Fabian Hulpia3, Eric Deconinck4, Serge Van Calenbergh3, Christophe P. Stove2
1Scientific Direction Epidemiology and Public Health, Section Lifestyle and Chronic Diseases, Belgian Early Warning System Drugs (BEWSD), Sciensano Brussels Belgium
2Laboratory of Toxicology, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium
3Laboratory for Medicinal Chemistry, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences Ghent University Ghent Belgium
4Scientific Direction Chemical and Physical Health Risks, Service of Medicines and Health Products, Sciensano Brussels Belgium

Tóm tắt

AbstractThis paper reports on the identification and full chemical characterization of isotonitazene (N,N‐diethyl‐2‐[5‐nitro‐2‐({4‐[(propan‐2‐yl)oxy]phenyl}methyl)‐1H‐benzimidazol‐1‐yl]ethan‐1‐amine), a potent NPS opioid and the first member of the benzimidazole class of compounds to be available on online markets. Interestingly, this compound was sold under the name etonitazene, a structural analog. Identification of isotonitazene was performed by gas chromatography mass spectrometry (GC–MS) and liquid chromatography time‐of‐flight mass spectrometry (LC‐QTOF‐MS), the latter identifying an exact‐mass m/z value of 411.2398. All chromatographic data indicated the presence of a single, highly pure compound. Confirmation of the specific benzimidazole regio‐isomer was performed using 1H and 13C NMR spectroscopy, after which the chemical characterization was finalized by recording Fourier‐transform (FT‐IR) spectra. A live cell‐based reporter assay to assess the in vitro biological activity at the μ‐opioid receptor (MOR) revealed that isotonitazene has a high potency (EC50 of 11.1 nM) and efficacy (Emax 180% of that of hydromorphone), thus confirming that this substance is a strong opioid. Isotonitazene has not been previously detected, either in powder form, or in biological fluids. The high potency and efficacy of isotonitazene, combined with the fact that this compound was being sold undiluted, represents an imminent danger to anyone aiming to use this powder.

Từ khóa


Tài liệu tham khảo

EMCDDA, 2013, Report on the Risk Assessment of 3,4‐Dichloro‐N‐{[1‐(dimethylamino)cyclohexyl]methyl}benzamide (AH‐7921) in the Framework of the Council Decision on New Psychoactive Substances

EMCDDA, 2014, Report on the Risk Assessment of MT‐45 in the Framework of the Council Decision on New Psychoactive Substances

10.1007/s11419-018-0413-1

10.3389/fphar.2018.00486

10.1208/s12248-017-0070-z

EMCDDA, 2019, European Drug Report 2019: Trends and Developments

AhmadF EscobedoL RossenL SpencerM WarnerM SuttonP.Provisional drug overdose death counts.2019;https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm. Accessed .

Hedegaard H, 1999, Drug overdose deaths in the United States, NCHS Data Brief, 2018, 1

10.1373/clinchem.2017.281626

10.1016/j.forsciint.2016.05.001

10.1007/s11419-019-00480-3

10.1007/s11419-018-0454-5

10.1016/S2215-0366(19)30218-4

10.3389/fphar.2018.00654

10.1007/BF02161117

10.1007/BF02161116

10.1021/jo2019416

Etat Francais.1‐Carbamoyl‐ and 1‐thiocarbamoyl‐3‐amino‐1 2 4‐triazoles.1963. GB patent 919458A.

HoffmannK HungerA KebrleJ RossiA.Analgetically active benzimidazoles.1959. DE patent 1057123B.

HoffmannK HungerA KebrleJ RossiA.New benzimidazoles.1962. CH patent 362080A.

HoffmannK HungerA RossiA.Benzimidazoles.1960. US patent 2935514A.

10.1111/j.2042-7158.1966.tb07782.x

10.1007/BF01486702

10.1007/BF00405575

10.1373/clinchem.2015.241315

IUPAC, 1997, Compendium of Chemical Terminology

General European OMCL Network (GEON).Qualification of Equipment Annex 4: Qualification of IR Spectrophotometers PA/PH/OMCL (18) 24 R1. European Directorate for the Quality of Medicines and Healthcare.2007. Accessed .

10.1373/clinchem.2018.289496

10.1021/acs.analchem.7b02552

10.1373/clinchem.2019.309443

10.1002/jms.4081

10.1016/j.ijms.2015.11.002

https://www.caymanchem.com/product/27255. Accessed 5 August 2019.

10.1002/hlca.19600430634

10.1002/hlca.19600430412

10.3109/15563657508990076

2003, Etonitazene in Brigham City, Utah, Microgram Bulletin, 36, 275

Sorokin VI, 1999, Etonitazene encountered in Moscow, Microgram Bulletin, 32, 239

Thông tin
Thông tin xuất bản

Drug Testing and Analysis

Tập 12 Số 4

422-430

Thông tin tác giả