Synthesis, Chemical Characterization, and μ-Opioid Receptor Activity Assessment of the Emerging Group of “Nitazene” 2-Benzylbenzimidazole Synthetic Opioids

UNODC, 2020, World Drug Report 2020, 20

UNODC, 2020, The Growing Complexity of the Opioid Crisis. Global SMART Update, Volume 24

EMCDDA, 2020, European Drug Report 2020: Trends and Developments

10.1016/S2215-0366(19)30218-4

Belgisch Staatsblad, 2017, Koninklijk Besluit Houdende Regeling van Verdovende Middelen, Psychotrope Stoffen

2020, S.3201—Temporary Reauthorization and Study of the Emergency Scheduling of Fentanyl Analogues Act

10.1002/dta.2738

10.1093/jat/bkaa066

10.1007/s00204-020-02855-7

10.1093/jat/bkaa094

10.1007/BF02161116

10.1002/hlca.19600430323

10.1002/hlca.19600430412

10.1002/hlca.19600430634

10.1002/hlca.19610440513

10.1002/hlca.19600430413

10.1002/hlca.19600430515

10.1007/BF02161117

Hoffmann, K., Hunger, A., Kebrle, J., and Rossi, A. (1959) Verfahren zur Herstellung analgetisch wirksamer Benzimidazole. DE Patent 1057123B.

Hoffmann, K., Hunger, A., and Rossi, A. (1960) Benzimidazoles. U.S. Patent 2935514A.

Hoffmann, K., Hunger, A., Kebrle, J., and Rossi, A. (1962) Verfahren zur Herstellung neuer Benzimidazole. CH Patent 362080A.

EMCDDA, 2020, Report on the Risk Assessment of N,N-Diethyl-2-[[4-(1-Methylethoxy)Phenyl]Methyl]-5-Nitro-1Hbenzimidazole- 1-Ethanamine (Isotonitazene) in Accordance with Article 5c of Regulation (EC) No 1920/2006 (as Amended)

10.1007/BF01486702

10.1021/acschemneuro.1c00037

10.3109/15563657508990076

Brandenberger H., 1974, Dtsch. Lebensm.-Rundsch., 70, 31

Morris, H. Synthetic opioids: the most addictive drugs in the world. https://www.vice.com/en/article/9bdymy/hamiltons-pharmacopeia-804-v16n4 (accessed Oct 26, 2020).

Reavy, P. Utah case of potent drug is U.S. first. https://www.deseret.com/2003/6/3/19726293/utah-case-of-potent-drug-is-u-s-first (accessed Oct 26, 2020).

Sorokin V. I., 1999, J. Clandestine Lab. Invest., 9, 20

Sorokin V. I., 1999, Microgram, 32, 239

10.1016/j.forsciint.2021.110686

Krotulski, A. J., and Logan, B. K. Isotonitazene. https://www.npsdiscovery.org/wp-content/uploads/2019/11/Isotonitazene_112119_ToxicologyAnalyticalReport.pdf (accessed Mar 10, 2020).

Krotulski, A. J., Papsun, D. M., Fogarty, M. F., Nelson, L., and Logan, B. K. Potent synthetic opioid - isotonitazene - recently identified in the Midwestern United States. https://www.npsdiscovery.org/wp-content/uploads/2019/11/Public-Alert_Isotonitazene_NPS-Discovery_111919-1.pdf (accessed Dec 1, 2019).

10.1093/jat/bkaa016

Mohr A. L., 2020, Toxicological Time Travel: Retrospective Datamining of Analytical Time-of-Flight Mass Spectrometry (TOFMS) Data for Evaluating the Rise and Fall of Novel Opioid and Fentanyl Analog Use in the United States

DEA. 21 CFR Part 1308. Schedules of Controlled Substances: Temporary Placement of Isotonitazene in Schedule I; 2020.

DEA, 21 CFR Part 1300.01 Definitions Relating to Controlled Substances

European Commission, 2020, Commission Delegated Directive (EU) 2020/1687 of 2 September 2020 Amending the Annex to Council Framework Decision 2004/757/JHA as Regards the Inclusion of the New Psychoactive Substance N,N-Diethyl-2-[[4-(1-Methylethoxy)Phenyl]Methyl]-5-Nitro-1H-Benzimidazole-1-Ethanamine (Isotonitazene) in the Definition of ‘Drug’

UNODC, 1975, The International Drug Control Conventions: Schedules of the Single Convention on Narcotic Drugs of 1961, as Amended by the 1972 Protocol

WHO. 43rd ECDD (2020): Critical review report: isotonitazene. https://www.who.int/docs/default-source/controlled-substances/43rd-ecdd/isonitazene-43rd-final-complete-a.pdf (accessed Feb 1, 2021).

Krotulski, A. J., Shuda, S. A., Fogarty, M. F., Decker, S. E., and Logan, B. K. Metonitazene. https://www.npsdiscovery.org/wp-content/uploads/2020/07/Metonitazene_073020_NMSLabs_Report.pdf (accessed Jul 30, 2020).

Krotulski, A. J., Papsun, D. M., Walton, S. E., and Logan, B. K. Public alert: Metonitazene begins proliferation as newest synthetic opioid among latest cycle of non-fentanyl related drugs. https://www.npsdiscovery.org/wp-content/uploads/2021/01/Public-Alert_Metonitazene_NPS-Discovery_012521.pdf (accessed Feb 1, 2021).

Krotulski, A. J., Perch, S., Walton, S. E., Fogarty, M. F., Papsun, D. M., and Logan, B. K. Butonitazene. https://www.npsdiscovery.org/wp-content/uploads/2021/01/Butonitazene_011521_ToxicologyAnalyticalReport.pdf (accessed Feb 25, 2021).

10.1007/s11419-020-00552-9

Schultz, J., Raje, S., Short, S., Stauffenberg, M., Krotulski, A. J., Fogarty, M. F., and Logan, B. K. Etodesnitazene. https://www.npsdiscovery.org/wp-content/uploads/2021/02/Etodesnitazene_022321_ToxicologyAnalyticalReport.pdf (accessed Feb 24, 2021).

10.1021/jm00237a024

10.1021/jo2019416

10.1021/ml200268w

10.1016/S0040-4039(97)01136-2

Bucha M., 2018, J. Heterocycl. Chem., 4, 321

10.1002/0471264180.or020.04

10.1016/j.ijms.2015.11.002

Cayman Chemical Company. Nitazenes. https://www.caymanchem.com/search?q=nitazene (accessed Oct 28, 2020).

10.1002/jms.4081

10.1016/j.neuropharm.2013.08.028

10.1016/j.tips.2020.09.009

10.1016/j.bcp.2019.08.025

10.1038/s41467-019-11875-6

10.1126/scisignal.aaz3140

10.1373/clinchem.2018.289496

10.1373/clinchem.2017.285361

10.1080/10408444.2019.1576588

10.1373/clinchem.2019.309443

10.1373/clinchem.2018.296905

10.1021/acschemneuro.8b00150

10.1038/s41580-018-0049-3

10.1016/j.bcp.2020.113910

10.1016/j.bcp.2020.114251

10.1021/acsptsci.9b00069

10.1124/mol.115.099630

10.1016/j.bcp.2020.113934

10.1007/s00210-008-0260-4

10.1124/mol.111.072801

10.1098/rspb.1983.0093

10.1124/mol.119.119214

10.1111/bph.13441

Ehlert F. J., 1999, J. Pharmacol. Exp. Ther., 289, 981

10.1124/jpet.107.120857