List of benzimidazole opioids

Last updated

Benzimidazole opioids, also known as nitazenes, are a class of synthetic opioids with an unusual benzimidazole structure often referred to as "opioid New Psychoactive Substances", or "opioid NPS". [1] [2] First synthesized in the 1950s by CIBA Pharmaceuticals as potential analgesic medications, several substances in the class have been identified, the best known being etonitazene. [1] Like other synthetic opioids, benzimidazole opioids bind the mu-opioid receptor and may exhibit potency up to several hundred times that of morphine. While several substances in this class have found applications in research, they have never been used in clinical medicine due to their profound risk of respiratory depression and death. [3] In the early 2020s, the substance has been recognized as emerging drugs of abuse. [4] [5] [6] Isotonitazine was first identified in samples of illicit drugs, and implicated in opioid overdose deaths in Europe, Canada, and the United States beginning in 2019. [7] Previously known nitazene analogs such as metonitazine and butonitazine, as well as novel nitazenes not previously patented, have since been discovered in toxicologic samples during forensic investigations. [6] Nitazene analogs have been found in pills missold as other drugs, such as benzodiazepines, in the United Kingdom [8] and New Zealand. [9]

Contents

Structure-activity relationship

The structure-activity relationship of the drug class has been explored to a reasonable extent. The optimal substitution pattern is fairly tightly defined (i.e. N,N-diethyl on the amine nitrogen, 4-ethoxy on the benzyl ring and 5-nitro on the benzimidazole ring), but even derivatives incorporating only some of these features are still potent opioids. If a methyl or carboxamide group is added on the alpha carbon of the benzyl group, or the benzyl is replaced by 2-phenylethyl, compounds of similar activity are obtained. Relative analgesic activity values are derived from tests on mice and cannot be extrapolated directly to humans, though the same general activity trends apply. [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [ excessive citations ]

A 2019 publication [22] has shown the possibility the previously assumed binding position of the benzimidazole class, [23] acting as a semi-rigid fentanyl analogue may be incorrect. Based on a large scale analysis of known opioid receptor ligands a template was created through manual overlaying and alignment which has identified several mu-specific areas within the receptor. In this analysis, it is noted, etonitazene now more closely matches another, separate mu-specific region, sharing only a small area in common with the fentanyl class.

Abuse

In the UK, nitazene abuse emerged in 2023 as an important cause of drug-overdose death, with it being linked to 54 deaths over a 6-month period. [24] Most of the deaths have occurred outside of 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.

Table of benzimidazole opioids

Nitazene general.png

Chemical structureDrug nameRing substitutionAnalgesic potency (morphine = 1)PubChemCAS number
DEAE-BN-BI structure.png Desnitazene (1-diethylaminoethyl-2-benzyl-benzimidazole)hydrogen0.1 28787 17817-67-3
Metodesnitazene structure.png Metodesnitazene (Metazene)4-methoxy1 26412 14030-77-4
1071546-40-1 (HCl)
Metodesnitazepyne structure.png Metodesnitazepyne4-methoxy
Etazene.svg Etodesnitazene (Etazene)4-ethoxy70 149797386 14030-76-3
Pyrrolidine-etodesnitazene structure.png Etodesnitazepyne4-ethoxy20 162623599
Piperidine-etodesnitazene structure.png Etodesnitazepipne4-ethoxy10 162623611 102762-98-1
Protodesnitazene structure.png Protodesnitazene4-(n-propoxy)10 157010653 805212-21-9
Isotodesnitazene structure.png Isotodesnitazene4-isopropoxy~75 162623708 2732926-27-9
Nitazene structure.png Nitazene hydrogen 2 15327524
Meta-metonitazene structure.png meta-Metonitazene3-methoxy2
Metonitazene.svg Metonitazene 4-methoxy 100 53316366 14680-51-4
Metonitazepyne structure.png Metonitazepyne4-methoxy
Metonitazepipne structure.png Metonitazepipne4-methoxy
N-Desethylmetonitazene structure.png N-Desethylmetonitazene4-methoxy
Metomethazene structure.png Metomethazene4-methoxy
Dimetonitazene structure.png Dimetonitazene3,4-dimethoxy10 162623836
Alpha-methyl-metonitazene structure.png α-methyl-metonitazene4-methoxy50 162625089 806634-80-0
Phenethyl-metonitazene structure.png Metonitazene phenethyl homologue (Ethylene metonitazene)4-methoxy50
Etonitazene.svg Etonitazene 4-ethoxy 1000-1500 13493 911-65-9
O-desmethyl-etonitazene structure.png O-Desethyl-etonitazene4-hydroxy 1 156588969 94758-81-3
N-desethyletonitazene structure.png N-Desethyletonitazene (NDE)4-ethoxy1000/1500-2000 162623580 2732926-26-8
5-Amino-etonitazene structure.png Etonitazene 5-amino metabolite4-ethoxy2 13408927
Etomethazene structure.png Etomethazene 4-ethoxy20 168310446 95293-25-7
Etotriflazene structure.png Etonitazene 5-trifluoromethyl analogue (Etotriflazene) [25] 4-ethoxy 21815908
Etocyanazene structure.png Etonitazene 5-cyano analogue (Etocyanazene) [26] 4-ethoxy 27268 15419-87-1
Etoacetazene structure.png Etonitazene 5-acetyl analogue (Etoacetazene) [27] 4-ethoxy 25957 13406-60-5
Etodicloazene structure.png Etonitazene 5,6-dichloro analogue (Etodicloazene)4-ethoxy
Dimethyl-etonitazene structure.png Etonitazene N,N-dimethyl analogue4-ethoxy20 67089584 714190-52-0
Etonitazepyne structure.png Etonitazepyne 4-ethoxy180-190 155804760 2785346-75-8
Piperidine-etonitazene structure.png Etonitazepipne 4-ethoxy190 [28] 162623834 734496-28-7
Morpholine-etonitazene structure.png Etonitazene morpholine analogue4-ethoxy2 162623685 805958-08-1
6-Nitro-etonitazene structure.png Etonitazene 6-nitro isomer (iso-etonitazene) [29] 4-ethoxy20 59799752 114160-61-1
Protonitazene structure.png Protonitazene 4-(n-propoxy)200 156589001 119276-01-6
95958-84-2
Protonitazepyne structure.png Protonitazepyne 4-(n-propoxy)180-190 168322728
Protonitazepipne structure.png Protonitazepipne4-(n-propoxy)
N-Desethylprotonitazene structure.png N-Desethylprotonitazene4-(n-propoxy)
Isotonitazene.svg Isotonitazene 4-isopropoxy500 145721979 14188-81-9
Isotonitazepyne structure.png Isotonitazepyne 4-isopropoxy 168322631
Isotonitazepipne structure.png Isotonitazepipne4-isopropoxy
N-desethyl-isotonitazene structure.png N-Desethylisotonitazene 4-isopropoxy1000-2000 162623899 2732926-24-6
Butonitazene structure.png Butonitazene 4-butoxy5 156588955 95810-54-1
Isobutylnitazene structure.png Isobutonitazene4-isobutoxy
Secbutylnitazene structure.png Secbutonitazene4-secbutoxy
Etoetonitazene structure.png Etoetonitazene 4-ethoxyethoxy50 162623504 806642-21-7
Fluonitazene structure.png Flunitazene 4-fluoro1 156588967 2728-91-8
Clonitazene Structural Formula V1.svg Clonitazene 4-chloro 3 62528 3861-76-5
Alpha-CONH2-clonitazene structure.png α-carboxamido-clonitazene4-chloro3
Bronitazene structure.png Bronitazene4-bromo5 162623726
Methylnitazene structure.png Methylnitazene (Menitazene)4-methyl 10 162623683 95282-00-1
Ethylnitazene structure.png Ethylnitazene (Enitazene)4-ethyl 20 162623845
Propylnitazene structure.png Propylnitazene (Pronitazene)4-propyl50 162623877 700342-00-3
Tbutylnitazene structure.png t-Butylnitazene4-(tert-butyl)2 162623621 805215-64-9
Acetoxynitazene structure.png Acetoxynitazene4-acetoxy 5 162623779 102760-24-7
Methylthionitazene structure.png Methylthionitazene4-methylthio50 162623790 102471-37-4
Ethylthionitazene structure.png Ethylthionitazene4-ethylthio30 162623931 102758-70-3
Phenylthio-etazene structure.png Etodesnitazene phenylthio analogue4-ethoxy1 21045
Phenylthio-etazene-pyrrolidine structure.png Etodesnitazene phenylthio / pyrrolidine analogue4-ethoxy2 19846499
Methylenedioxynitazene structure.png Methylenedioxynitazene [30] 3,4-methylenedioxy
Tetrahydrofuranitazene structure.png Tetrahydrofuranitazene (Ethyleneoxynitazene) [31] fused tetrahydrofuran

See also

Related Research Articles

<span class="mw-page-title-main">Etonitazene</span> Chemical compound

Etonitazene, also known as EA-4941 or CS-4640, is a benzimidazole opioid, first reported in 1957, that has been shown to have approximately 1,000 to 1,500 times the potency of morphine in animals.

<span class="mw-page-title-main">Ketobemidone</span> Chemical compound

Ketobemidone, sold under the brand name Ketogan among others, is a powerful synthetic opioid painkiller. Its effectiveness against pain is in the same range as morphine, and it also has some NMDA-antagonist properties imparted, in part, by its metabolite norketobemidone. This may make it useful for some types of pain that do not respond well to other opioids. It is marketed in Denmark, Iceland, Norway and Sweden and is used for severe pain.

<span class="mw-page-title-main">3-Methylfentanyl</span> Opioid analgesic

3-Methylfentanyl is an opioid analgesic that is an analog of fentanyl. 3-Methylfentanyl is one of the most potent opioids, estimated to be between 400 and 6000 times stronger than morphine, depending on which isomer is used.

<span class="mw-page-title-main">Metofoline</span> Chemical compound

Metofoline (INN), also known as methofoline (USAN), is an opioid analgesic drug discovered in the 1950s by a team of Swiss researchers at Hoffmann-La Roche.

<span class="mw-page-title-main">Clonitazene</span> Opioid analgesic

Clonitazene is an opioid analgesic of approximately three times the potency of morphine. It is related to etonitazene, an opioid of significantly higher potency. Clonitazene is not currently marketed. It is a controlled substance; in the United States it is a Schedule I Narcotic controlled substance with a DEA ACSCN of 9612 and an established manufacturing quota of 25 grams for 2022.

<span class="mw-page-title-main">BDPC</span> Synthetic opioid

BDPC is a potent fully synthetic opioid with a distinctive arylcyclohexylamine chemical structure. It was developed by Daniel Lednicer at Upjohn in the 1970s. Initial studies estimated that it was around 10,000 times the potency of morphine in animal models. However, later studies using more modern techniques assigned a value of 504 times the potency of morphine for the more active trans-isomer. This drug was first seized along with three kilograms of acetylfentanyl in an April 25, 2013 police action in Montreal, Canada, and has reportedly continued to be available on the designer drug market internationally. Analogues where the para-bromine is replaced by chlorine or a methyl group retain similar activity, while the meta-hydroxyl derivative demonstrated robust antagonist activity.

<span class="mw-page-title-main">Metonitazene</span> Chemical compound (analgesic drug)

Metonitazene is an analgesic compound related to etonitazene, which was first reported in 1957, and has been shown to have approximately 1000 times the potency of morphine by central routes of administration, but if used orally it has been shown to have approximately 10 times the potency of morphine.

<span class="mw-page-title-main">Gestonorone acetate</span> Chemical compound

Gestonorone acetate, or gestronol acetate, also known as norhydroxyprogesterone acetate, is a progestin of the 19-norprogesterone and 17α-hydroxyprogesterone groups which was developed in the early 1960s but was never marketed. It is the C17α acetate ester of gestronol (17α-hydroxy-19-norprogesterone).

<span class="mw-page-title-main">Isotonitazene</span> Chemical compound

Isotonitazene is a benzimidazole-derived opioid analgesic drug related to etonitazene, which has been sold as a designer drug. It has only around half the potency of etonitazene in animal studies, but it is likely even less potent in humans as was seen with etonitazene. Isotonitazene was fully characterized in November 2019 in a paper where the authors performed a full analytical structure elucidation in addition to determination of the potency at the μ-opioid receptor using a biological functional assay in vitro. While isotonitazene was not compared directly to morphine in this assay, it was found to be around 2.5 times more potent than hydromorphone and slightly more potent than fentanyl.

<span class="mw-page-title-main">Brorphine</span> Chemical compound

Brorphine is a piperidine-based opioid analgesic compound. Brorphine was originally discovered in a 2018 paper investigating functionally biased opioid compounds, with the intention of finding safer analgesics that produce less respiratory depression than typical opioids. Brorphine was originally reported to be highly biased, with an EC50 of 4.8nM for GTPγS binding and 182nM for β-arrestin recruitment, however a more recent study found no significant bias for any of the compounds tested, including brorphine. Its safety profile in any animal model has never been established. Despite the lack of safety information on the compound, brorphine has been sold as a designer drug since mid-2019, initially being identified in the US Midwest, though it has since been found in 2020 in Belgium. It is related in chemical structure to compounds such as benzylfentanyl and bezitramide, though it is sufficiently structurally distinct to fall outside the formal definition of a "fentanyl analogue" in jurisdictions such as the US and New Zealand which have Markush structure controls over this family of drugs.

<span class="mw-page-title-main">Etodesnitazene</span> Chemical compound

Etodesnitazene is a benzimidazole derived opioid analgesic drug, which was originally developed in the late 1950s alongside etonitazene and a range of related derivatives. It is many times less potent than etonitazene itself, but still 70x more potent than morphine in animal studies. Corresponding analogues where the N,N-diethyl group is replaced by piperidine or pyrrolidine rings also retain significant activity. Etodesnitazene has been sold as a designer drug, first being identified in both Poland and Finland in March 2020.

<span class="mw-page-title-main">Etonitazepipne</span> Benzimidazole derivative

Etonitazepipne is a benzimidazole derivative with opioid effects around 100 times more potent than morphine, which has been sold over the internet as a designer drug.

<span class="mw-page-title-main">Metodesnitazene</span> Chemical compound

Metodesnitazene is a benzimidazole derivative with opioid effects, though unlike related compounds such as metonitazene and etodesnitazene which are quite potent, metodesnitazene is only around the same potency as morphine in animal studies. It is illegal in both the US and UK.

<span class="mw-page-title-main">Butonitazene</span> Chemical compound

Butonitazene is a benzimidazole derivative with opioid effects, which has been sold over the internet as a designer drug. It has relatively low potency compared to many related compounds, and has generally been encountered as a component of mixtures with other substances rather than in its pure form. However, it is still several times the potency of morphine and has been implicated in several cases of drug overdose. Butonitazene is a Schedule I drug in the US, along with several related compounds.

<span class="mw-page-title-main">N-Desethylisotonitazene</span> Chemical compound

N-Desethylisotonitazene (norisotonitazene) is a benzimidazole opioid with potent analgesic effects which has been sold as a designer drug. It was first identified in 2023 as an active metabolite of the closely related compound isotonitazene, and was found to have similar potency. It is one of the strongest benzimidazole opioids discovered, with an analgesic strength 20 times stronger than fentanyl.

<i>N</i>-Desethyletonitazene Chemical compound

N-Desethyletonitazene is a benzimidazole derivative with potent opioid effects which has been sold as a designer drug. It is better known as an active metabolite of the related compound etonitazene, but has similar activity to the parent compound and has sometimes appeared as a drug of abuse in its own right, being identified in New Zealand in 2024.

<span class="mw-page-title-main">Etonitazene 5-acetyl analogue</span> Chemical compound

Etonitazene 5-acetyl analogue (Etoacetazene, 5-acetyldesnitroetonitazene) is a benzimidazole derivative with opioid effects, first developed in the 1950s as part of the research that led to better-known compounds such as etonitazene. It is an analogue of etonitazene where the 5-nitro (NO2) group has been replaced by an acetyl (COCH3) group. It is described as having "reduced but still significant" potency compared to etonitazene itself. This compound was also tested as part of a series of cannabinoid receptor 2 agonists, and was found to be active though with fairly low potency of 960 nM at CB2, and negligible activity at CB1.

<span class="mw-page-title-main">Etonitazene 5-cyano analogue</span> Chemical compound

Etonitazene 5-cyano analogue (Etocyanazene, 5-cyanodesnitroetonitazene) is a benzimidazole derivative with opioid effects, first developed in the 1950s as part of the research that led to better-known compounds such as etonitazene. It is an analogue of etonitazene where the 5-nitro (NO2) group has been replaced by a nitrile (C≡N) group. It is described as having "reduced but still significant" potency compared to etonitazene itself. It was made illegal in Germany in July 2021.

<span class="mw-page-title-main">Etoetonitazene</span> Chemical compound

Etoetonitazene is a benzimidazole derivative with opioid effects, first developed in the 1950s as part of the research that led to better-known compounds such as etonitazene. It is an analogue of etonitazene where the ethoxy sidechain has been extended to ethoxyethoxy. It is less potent than other benzimidazole class opioids, but is still a potent mu opioid receptor agonist with around 50x the potency of morphine, and has been sold as a designer drug since around 2022.

<span class="mw-page-title-main">Flunitazene</span> Designer drug with opioid effects

Flunitazene (Fluonitazene) is a benzimidazole derivative with opioid effects, first developed in the 1950s as part of the research that led to better-known compounds such as etonitazene. It is one of the least potent derivatives from this class to have appeared as a designer drug, with only around the same potency as morphine, but nevertheless has been sold since around 2020, and has been linked to numerous drug overdose cases.

References

  1. 1 2 Pergolizzi Jr J, Raffa R, LeQuang JA, Breve F, Varrassi G (2023). "Old Drugs and New Challenges: A Narrative Review of Nitazenes". Cureus. 15 (6): e40736. doi: 10.7759/cureus.40736 . ISSN   2168-8184. PMC   10361140 . PMID   37485167.
  2. ↑ Ujváry I, Christie R, Evans-Brown M, Gallegos A, Jorge R, de Morais J, et al. (April 2021). "DARK Classics in Chemical Neuroscience: Etonitazene and Related Benzimidazoles". ACS Chemical Neuroscience. 12 (7): 1072–1092. doi:10.1021/acschemneuro.1c00037. PMID   33760580. S2CID   232356192.
  3. ↑ 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.
  4. ↑ USpatent 2935514,Hoffman K, Hunger A,"BENZMDAZOLES (sic)",published 1960-05-03, assigned to Ciba Pharmaceutical Products Inc.
  5. ↑ Drug Enforcement Administration (June 2021). "Benzimidazole Opioids" (PDF). Retrieved 6 January 2022.
  6. 1 2 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.
  7. ↑ 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.
  8. ↑ Lanes R. "PHILTRE Annual Report April 2022 - March 2023" (PDF). WEDINOS. Retrieved 1 July 2024.
  9. ↑ "Potent opioid found in fake diazepam". The Level NZ. April 19, 2024. Retrieved 1 July 2024.
  10. ↑ US 2944062,Hoffman K, Hunger A,"Certain Alpha (1-diethylaminoethyl (2), Alpha Aryl Acetamides",issued 5 July 1960, assigned to Ciba Pharma Products Inc.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ 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.
  20. ↑ 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.
  21. ↑ 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.
  22. ↑ Wu Z, Hruby VJ (October 2019). "Toward a Universal μ-Agonist Template for Template-Based Alignment Modeling of Opioid Ligands". ACS Omega. 4 (17): 17457–17476. doi: 10.1021/acsomega.9b02244 . PMC   6812133 . PMID   31656918.
  23. ↑ Beckett AH, Casy AF (February 1965). "Analgesics and their antagonists: biochemical aspects and structure-activity relationships". Progress in Medicinal Chemistry. 4: 171–218. doi:10.1016/s0079-6468(08)70169-3. ISBN   9780444533234. PMID   5319798.
  24. ↑ Homer A, Johal N (11 December 2023). "Street drugs stronger than heroin linked to 54 deaths in UK". BBC News.
  25. ↑ 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.
  26. ↑ Lecolier S, Trouiller G (1967). "Nouveaux benzimidazoles doués d'activité morphinique" [New benzimidazoles with opioid activity.]. Chim. Ther. (in French). 2: 16–24.
  27. ↑ "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.
  28. ↑ 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. doi:10.1007/s00204-022-03294-2. hdl: 1854/LU-8751259 . PMID   35449307.
  29. ↑ 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.
  30. ↑ "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.
  31. ↑ "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.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.