List of benzimidazole opioids

Benzimidazole core structure

Benzimidazole opioids are a class of synthetic opioids that contain a benzimidazole core structure. The pain-relieving properties of these substances were discovered in the mid-1950s by the Swiss company Ciba AG. The most important subgroup are the nitazene opioids, which since 2019 have become increasingly widespread as narcotics in North America and Europe. Due to unacceptable side effects like respiratory depression, there is no medical use for benzimidazole opioids.[1]

## History

[edit]

Desnitazene

In 1957, the pharmaceutical research department of Ciba AG published the discovery of the (low) analgesic effect of 1-(β-diethylaminoethyl)-2-benzylbenzimidazole (desnitazene).[2] Shortly afterwards, the nitazenes were discovered in structure-activity relationship studies.[3][4]

## Structure-activity relationship

[edit]

The class of substances is defined chemically by the presence of the benzimidazole core structure and pharmacologically by opioid activity. The compounds are derived from the historical prototype 1-(β-diethylaminoethyl)-2-benzylbenzimidazole (desnitazene). The replacement of the N,N-dialkylamino unit by pyrrolidinyl or piperidinyl, which is found in nitazepyne and nitazepipne compounds, falls into the spectrum of designer drugs. Substitution of the benzyl for thienylmethyl, pyridylmethyl, α-napthylmethyl or styryl has a potency-reducing effect.[5][6] Substitution in position 4 of the benzyl affects analgesic potency in the following order: ethoxy > isopropyloxy > n-propyloxy > methoxy > methylthio > H/Cl/F > hydroxy. The most potent of the known compounds contain a nitro group in position 5.[6] The replacement of benzimidazole with an indole has been known from studies conducted by Ciba AG since 1963.[7]

Relative analgesic activity values are derived from tests on mice and cannot be extrapolated directly to humans, though the same general activity trends apply.[8][9][10][11][12][13][14][15][16][17][18][excessive citations]

Like other synthetic opioids, benzimidazole opioids bind the mu-opioid receptor and may exhibit potency up to several hundred times that of morphine.[19][20][21][22][23]

## Prevalence

[edit]

In the early 2020s, the substances have been recognized as emerging drugs of abuse.[24][25] Isotonitazene was first identified in samples of illicit drugs, and implicated in opioid overdose deaths in Europe, Canada, and the United States in March and April 2019.[26] Previously known nitazene analogs such as metonitazene and butonitazene, as well as novel nitazenes not previously described in the scientific or patent literature, have since been discovered in toxicologic samples during forensic investigations.[25] Nitazenes have been found in pills missold as other drugs, such as benzodiazepines, in the United Kingdom[27] and New Zealand.[28]

In the UK, abuse of nitazene analogues emerged in 2023 as an important cause of drug-overdose death, with it being linked to 54 deaths over a 6-month period.[29] Most of the deaths have occurred outside London, the source of supply is thought to be by post from laboratories in China and some of the deaths have been associated by the mislabelling of nitazenes as fentanyl. Most cases of abuse and overdose are linked to potent derivatives such as metonitazene, protonitazene, isotonitazene, etonitazepyne, and etodesnitazene.

## Table of benzimidazole opioids

[edit]

Structure  | Name  | Ring sub.  | Analgesic potency (morphine = 1)  | PubChem  | CAS #

|
|
|
|
|

| Desnitazene (1-diethylaminoethyl-2-benzyl-benzimidazole)  | hydrogen  | 0.1  | 28787 | 17817-67-3
| Metodesnitazene (Metazene)  | 4-methoxy  | 1  | 26412 | 14030-77-4
1071546-40-1 (HCl)
| Metodesnitazepyne | 4-methoxy  |  |  |
| Etodesnitazene (Etazene)  | 4-ethoxy  | 70  | 149797386 | 14030-76-3
| Etodesnitazepyne | 4-ethoxy  | 20  | 162623599 |
| Etodesnitazepipne | 4-ethoxy  | 10  | 162623611 | 102762-98-1
| Protodesnitazene | 4-(n-propoxy)  | 10  | 157010653 | 805212-21-9
| Isotodesnitazene | 4-isopropoxy  | ~75  | 162623708 | 2732926-27-9
| Nitazene  | hydrogen | 2  | 15327524 | 14030-71-8
| Ethylene nitazene  | hydrogen  |  | 15327525 | 194537-85-4
| meta-Metonitazene | 3-methoxy  | 2  |  | 96168-49-9
| Metonitazene | 4-methoxy | 100  | 53316366 | 14680-51-4
| Metonitazepyne | 4-methoxy |  |  | 3053113-16-6
| Metonitazepipne | 4-methoxy |  |  |
| N-Desethylmetonitazene | 4-methoxy |  |  |
| Metomethazene | 4-methoxy |  |  | 95138-58-2
| Dimetonitazene | 3,4-dimethoxy  | 10  | 162623836 | 95809-33-9
| α-methyl-metonitazene | 4-methoxy  | 50  | 162625089 | 806634-80-0
| α-methyl-etonitazene  | 4-ethoxy  |  |  |
| α-hydroxy-etonitazene  | 4-ethoxy  |  | 21815907 |
| Metonitazene phenethyl homologue (Ethylene metonitazene)  | 4-methoxy  | 50  |  |
| Ethylene etonitazene  | 4-ethoxy  |  |  |
| Etonitazene | 4-ethoxy | 1000-1500  | 13493 | 911-65-9
| O-Desethyl-etonitazene | 4-hydroxy | 1  | 156588969 | 94758-81-3
| N-Desethyletonitazene (NDE)  | 4-ethoxy  | 1000/1500-2000  | 162623580 | 2732926-26-8
| Etonitazene 5-amino metabolite | 4-ethoxy  | 2  | 13408927 | 75821-80-6
| Etomethazene | 4-ethoxy  | 20  | 168310446 | 95293-25-7
| Etonitazene 5-trifluoromethyl analogue (Etotriflazene)[30] | 4-ethoxy  |  | 21815908 | 15451-92-0
| 5-Trifluoromethyl isotodesnitazene  | 4-isopropoxy  |  |  | 15451-92-0
| Etonitazene 5-cyano analogue (Etocyanazene) [31] | 4-ethoxy  |  | 27268 | 15419-87-1
| Etonitazene 5-acetyl analogue (Etoacetazene) [32] | 4-ethoxy  |  | 25957 | 13406-60-5
| Etonitazene 5,6-dichloro analogue (Etodicloazene)  | 4-ethoxy  |  |  | 102476-04-0
| Etonitazene N,N-dimethyl analogue | 4-ethoxy  | 20  | 67089584 | 714190-52-0
| Etonitazepyne | 4-ethoxy  | 180-190  | 155804760 | 2785346-75-8
| Etonitazepipne | 4-ethoxy  | 190 [33] | 162623834 | 734496-28-7
| Etonitazene morpholine analogue  | 4-ethoxy  | 2  | 162623685 | 805958-08-1
| 1-Ethyl pyrrolidinylmethyl N-desalkyl etonitazene  | 4-ethoxy  |  |  |
| Etonitazene 6-nitro isomer (iso-etonitazene) [34] | 4-ethoxy  | 20  | 59799752 | 114160-61-1
| Protonitazene | 4-(n-propoxy)  | 200  | 156589001 | 119276-01-6
95958-84-2
| Protonitazepyne | 4-(n-propoxy)  | 180-190  | 168322728 |
| Protonitazepipne | 4-(n-propoxy)  |  |  |
| N-Desethylprotonitazene | 4-(n-propoxy)  |  |  |
| Isotonitazene | 4-isopropoxy  | 500  | 145721979 | 14188-81-9
| Isotonitazepyne | 4-isopropoxy  |  | 168322631 |
| Isotonitazepipne | 4-isopropoxy  |  |  |
| N-Desethylisotonitazene | 4-isopropoxy  | 1000-2000  | 162623899 | 2732926-24-6
| iso-isotonitazene  | 4-isopropoxy  |  |  |
| Butonitazene | 4-butoxy  | 5  | 156588955 | 95810-54-1
| Isobutonitazene | 4-isobutoxy  |  | 168322282 |
| Secbutonitazene | 4-secbutoxy  |  | 168322285 |
| Etoetonitazene | 4-ethoxyethoxy  | 50  | 162623504 | 806642-21-7
| Fluornitrazene [35] | 4-(2-fluoroethoxy)  |  | 172332078 |
| Trifluorometonitazene  | 4-trifluoromethoxy  |  |  | 954386-78-8
| Flunitazene | 4-fluoro  | 1  | 156588967 | 2728-91-8
| Clonitazene | 4-chloro | 3  | 62528 | 3861-76-5
| Diclonitazene | 2,4-dichloro |  |  |
| α-carboxamido-clonitazene | 4-chloro  | 3  |  |
| Bronitazene | 4-bromo  | 5  | 162623726 |
| Nitronitazene | 4-nitro  |  |  | 101795-25-9
| Methylnitazene (Menitazene)  | 4-methyl | 10  | 162623683 | 95282-00-1
| Ethylnitazene (Enitazene)  | 4-ethyl | 20  | 162623845 | 114160-82-6
| Propylnitazene (Pronitazene)  | 4-propyl  | 50  | 162623877 | 700342-00-3
| t-Butylnitazene | 4-(tert-butyl)  | 2  | 162623621 | 805215-64-9
| Acetoxynitazene | 4-acetoxy | 5  | 162623779 | 102760-24-7
| Methionitazene | 4-methylthio  | 50  | 162623790 | 102471-37-4
| Ethylthionitazene | 4-ethylthio  | 30  | 162623931 | 102758-70-3
| Etodesnitazene phenylthio analogue | 4-ethoxy  | 1  | 21045 | 3275-92-1
| Etodesnitazene phenylthio / pyrrolidine analogue | 4-ethoxy  | 2  | 19846499 | 13451-68-8
| Methylenedioxynitazene[36] | 3,4-methylenedioxy  |  |  |
| Ethyleneoxynitazene[37] | fused tetrahydrofuran  |  |  |

## See also

[edit]

* 25-NB
* Arylcyclohexylamine
* Kush (drug)
* List of aminorex analogues
* List of benzodiazepines
* List of fentanyl analogues
* List of phenyltropanes
* Utopioid

## References

[edit]

1. ^ Montanari E, Madeo G, Pichini S, Busardò FP, Carlier J (August 2022). "Acute Intoxications and Fatalities Associated With Benzimidazole Opioid (Nitazene Analog) Use: A Systematic Review". Therapeutic Drug Monitoring. 44 (4): 494–510\. doi:10.1097/FTD.0000000000000970. PMID 35149665. S2CID 246776288.
2. ^ Hunger A, Kebrle J, Rossi A, Hoffmann K (1957). "Synthesis of basic substituted, analgesically active benzimidazole derivatives". Experientia. 13 (10): 400–1\. doi:10.1007/BF02161116. PMID 13473817.`{{cite journal}}`: CS1 maint: multiple names: authors list (link)
3. ^ US patent 2935514, Hoffman K, Hunger A, "BENZMDAZOLES (sic)", published 1960-05-03, assigned to Ciba Pharmaceutical Products Inc.
4. ^ Drug Enforcement Administration (June 2021). "Benzimidazole Opioids" (PDF). Retrieved 6 January 2022.
5. ^ Hunger A, Kebrle J, Rossi A, and Hoffmann K: ″Benzimidazole-Derivate und verwandte Heterocyclen III. Synthese von 1-Aminoalkyl-2-benzyl-nitro-benzimidazolen.″ Helv. Chim. Acta 1960, 43, 1032–1046, doi:10.1002/hlca.19600430412.
6. ^ a b Ujváry I, Christie R, Evans-Brown M, Gallegos A, Jorge R, de Morais J, et al. (2021). "DARK Classics in Chemical Neuroscience: Etonitazene and Related Benzimidazoles". ACS Chem Neurosci. 12 (7): 1072–1092\. doi:10.1021/acschemneuro.1c00037. PMID 33760580.
7. ^ Kebrle H, Hoffmann K: ″Synthesis of indole derivatives by substitution in the α-position.″ Gazzetta Chimica Italiana 1963, 93, 238–243.
8. ^ Gross F, Turrian H (October 1957). "[Benzimidazole derivatives with strong analgesic effects]". Experientia. 13 (10): 401–3\. doi:10.1007/BF02161117. PMID 13473818. S2CID 6824038.
9. ^ Renton P, Green B, Maddaford S, Rakhit S, Andrews JS (March 2012). "NOpiates: Novel Dual Action Neuronal Nitric Oxide Synthase Inhibitors with μ-Opioid Agonist Activity". ACS Medicinal Chemistry Letters. 3 (3): 227–31\. doi:10.1021/ml200268w. PMC 4025805. PMID 24900459.
10. ^ Hunger A, Kebrle J, Rossi A, Hoffmann K (October 1957). "[Synthesis of analgesically active benzimidazole derivatives with basic substitutions]" [Synthesis of analgesically active benzimidazole derivatives with basic substitutions]. Experientia. 13 (10): 400–1\. doi:10.1007/BF02161116. PMID 13473817. S2CID 32179439.
11. ^ Rossi A, Hunger A, Kebrle J, Hoffmann K (1960). "Benzimidazol-Derivate und verwandte Heterocyclen. IV. Die Kondensation von o-Phenylendiamin mit α-Aryl- und γ-Aryl-acetessigester" [Benzimidazole derivatives and related heterocycles IV. The condensation of o-phenylenediamine with α-aryl and γ-aryl-acetoacetate]. Helvetica Chimica Acta (in German). 43 (4): 1046–1056\. doi:10.1002/hlca.19600430413.
12. ^ Rossi A, Hunger A, Kebrle J, Hoffmann K (1960). "Benzimidazol-Derivate und verwandte Heterocyclen V. Die Kondensation von o-Phenylendiamin mit aliphatischen und alicyclischen β-Ketoestern" [Benzimidazole derivatives and related heterocycles V. The condensation of o-phenylenediamine with aliphatic and alicyclic β-keto esters]. Helvetica Chimica Acta (in German). 43 (5): 1298–1313\. doi:10.1002/hlca.19600430515.
13. ^ Hunger A, Kebrle J, Rossi A, Hoffmann K (1960). "Benzimidazol-Derivate und verwandte Heterocyclen VI. Synthese von Phenyl-[1-aminoalkyl-benzimidazolyl-(2)]-essigsäure-estern und -amiden" [Benzimidazole derivatives and related Heterocycles VI. Synthesis of phenyl-[1-aminoalkyl-benzimidazolyl-(2)]-acetic acid esters and amides]. Helvetica Chimica Acta (in German). 43 (6): 1727–1733\. doi:10.1002/hlca.19600430634.
14. ^ Hunger A, Kebrle J, Rossi A, Hoffmann K (1961). "Benzimidazol-Derivate und verwandte Heterocyclen VII. Synthese neuer 2-Amino-benzimidazole" [Benzimidazole Derivatives and related Heterocycles VII. Synthesis of new 2-amino-benzimidazole]. Helvetica Chimica Acta (in German). 44 (5): 1273–1282\. doi:10.1002/hlca.19610440513.
15. ^ Gross F, Turrian H (October 1957). "[Benzimidazole derivatives with strong analgesic effects]" [Benzimidazole derivatives with strong analgesic effects]. Experientia. 13 (10): 401–3\. doi:10.1007/BF02161117. PMID 13473818. S2CID 6824038.
16. ^ Seki T, Sasajima M, Watanbe Y, Nakajima K (March 1967). "[Studies on 2-benzimidazolethiol derivatives. N. Analgesic effect and pharmacological property of 1-(2-diethylaminoethyl)-2-(p-ethoxyphenylthio)benzimidazole hydrochloride]". Yakugaku Zasshi (in Japanese). 87 (3): 296–301\. doi:10.1248/yakushi1947.87.3_296. PMID 6069375.
17. ^ Seki T (March 1967). "[Studies on 2-benzimidazolethiol derivatives. V. Structure-activity relationship on analgesic action of 1-(dialkylamino-alkyl)-2-(p-ethoxyphenylthio)benzimidazole]". Yakugaku Zasshi (in Japanese). 87 (3): 301–9\. doi:10.1248/yakushi1947.87.3_301. PMID 6069376.
18. ^ Seki T, Watanabe Y (May 1969). "[Studies on 2-benzimidazolethiol derivatives. VI. Synthesis and analgesic effect of 1-(2-diethylaminoethyl)-2-(p-ethoxyphenylthio)-5-substituted benzimidazole]". Yakugaku Zasshi (in Japanese). 89 (5): 617–26\. doi:10.1248/yakushi1947.89.5_617. PMID 5817995.
19. ^ Glatfelter GC, Vandeputte MM, Chen L, Walther D, Tsai MM, Shi L, et al. (December 2023). "Alkoxy chain length governs the potency of 2-benzylbenzimidazole 'nitazene' opioids associated with human overdose". Psychopharmacology. 240 (12): 2573–2584\. doi:10.1007/s00213-023-06451-2. PMID 37658878.
20. ^ Tsai MM, Chen L, Baumann MH, Canals M, Javitch JA, Lane JR, et al. (February 2024). "In Vitro Functional Profiling of Fentanyl and Nitazene Analogs at the μ-Opioid Receptor Reveals High Efficacy for Gi Protein Signaling". ACS Chemical Neuroscience. 15 (4): 854–867\. doi:10.1021/acschemneuro.3c00750. PMC 11890208. PMID 38345920.
21. ^ Kozell LB, Eshleman AJ, Wolfrum KM, Swanson TL, Bloom SH, Benware S, et al. (April 2024). "Pharmacologic Characterization of Substituted Nitazenes at μ, κ, and Δ Opioid Receptors Suggests High Potential for Toxicity". The Journal of Pharmacology and Experimental Therapeutics. 389 (2): 219–228\. doi:10.1124/jpet.123.002052. PMC 11026150. PMID 38453524.
22. ^ Kanamori T, Okada Y, Segawa H, Yamamuro T, Kuwayama K, Tsujikawa K, Iwata YT. Analysis of highly potent synthetic opioid nitazene analogs and their positional isomers. Drug Test Anal. 2023 Apr;15(4):449-457. doi:10.1002/dta.3415 PMID 36437623
23. ^ Vandeputte MM, Glatfelter GC, Walther D, Layle NK, St Germaine DM, Ujváry I, Iula DM, Baumann MH, Stove CP. Characterization of novel nitazene recreational drugs: Insights into their risk potential from in vitro μ-opioid receptor assays and in vivo behavioral studies in mice. Pharmacol Res. 2024 Nov 7;210:107503. doi:10.1016/j.phrs.2024.107503 PMID 39521025
24. ^ Drug Enforcement Administration (June 2021). "Benzimidazole Opioids" (PDF). Retrieved 6 January 2022.
25. ^ a b Walton SE, Krotulski AJ, Logan BK (March 2022). "A Forward-Thinking Approach to Addressing the New Synthetic Opioid 2-Benzylbenzimidazole Nitazene Analogs by Liquid Chromatography-Tandem Quadrupole Mass Spectrometry (LC-QQQ-MS)". Journal of Analytical Toxicology. 46 (3): 221–231\. doi:10.1093/jat/bkab117. PMC 8935987. PMID 34792157.
26. ^ European Monitoring Centre for Drugs Drug Addiction (2020-11-13). "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)". European Monitoring Centre for Drugs and Drug Addiction. Publications Office of the European Union. doi:10.2810/107576. ISBN 9789294974952. Retrieved 9 May 2022.
27. ^ Lanes R. "PHILTRE Annual Report April 2022 - March 2023" (PDF). WEDINOS. Retrieved 1 July 2024.
28. ^ "Potent opioid found in fake diazepam". The Level NZ. April 19, 2024. Retrieved 1 July 2024.
29. ^ Homer A, Johal N (11 December 2023). "Street drugs stronger than heroin linked to 54 deaths in UK". BBC News.
30. ^ Tonelli M, Cichero E, Mahmoud AM, Rabbito A, Tasso B, Fossa P, et al. (December 2018). "Exploring the effectiveness of novel benzimidazoles as CB2 ligands: synthesis, biological evaluation, molecular docking studies and ADMET prediction". MedChemComm. 9 (12): 2045–2054\. doi:10.1039/c8md00461g. PMC 6301267. PMID 30647880.
31. ^ Lecolier S, Trouiller G (1967). "Nouveaux benzimidazoles doués d'activité morphinique" [New benzimidazoles with opioid activity.]. Chim. Ther. (in French). 2: 16–24.
32. ^ "A review of the evidence on the use and harms of 2-benzyl benzimidazole ('nitazene') and piperidine benzimidazolone ('brorphine-like') opioids" (PDF). Advisory Council on the Misuse of Drugs. UK. July 2022.
33. ^ Vandeputte MM, Verougstraete N, Walther D, Glatfelter GC, Malfliet J, Baumann MH, et al. (June 2022). "First identification, chemical analysis and pharmacological characterization of N-piperidinyl etonitazene (etonitazepipne), a recent addition to the 2-benzylbenzimidazole opioid subclass". Archives of Toxicology. 96 (6): 1865–1880\. Bibcode:2022ArTox..96.1865V. doi:10.1007/s00204-022-03294-2. hdl:1854/LU-8751259. PMID 35449307.
34. ^ Kanamori T, Okada Y, Segawa H, Yamamuro T, Kuwayama K, Tsujikawa K, et al. (November 2022). "Analysis of highly potent synthetic opioid nitazene analogs and their positional isomers". Drug Testing and Analysis. 15 (4): 449–457\. doi:10.1002/dta.3415. PMID 36437623. S2CID 254042990.
35. ^ Michaelides M, et al. Fluorinated Mu-Opioid Receptor Agonists. WO 2024/196438
36. ^ "Fourth addendum to ACMD report on the use and harms of 2-benzyl benzimidazole ('nitazene') and piperidine benzimidazolone ('brorphine-like') opioids" (PDF). Advisory Council on the Misuse of Drugs. 5 April 2024.
37. ^ "Third addendum to ACMD report on the use and harms of 2-benzyl benzimidazole ('nitazene') and piperidine benzimidazolone ('brorphine-like') opioids" (PDF). Advisory Council on the Misuse of Drugs. 15 December 2023.

* v
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Chemical classes of psychoactive drugs

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