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

Blanckaert, Peter; Cannaert, Annelies; Uytfanghe, Katleen Van; Hulpia, Fabian; Deconinck, Éric; Calenbergh, Serge Van

doi:10.1002/dta.2738

Cited by 78 publications

(96 citation statements)

References 25 publications

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“…S7) displayed bands that could be attributed to the characteristic elements of the etazene structure, such as benzimidazole ring (sharp bands at 762-1609 cm −1 ), methylene bridges (1466 cm −1 ), aliphatic-aryl ethers (1259 cm −1 ), aromatic systems (1600-2000 cm −1 ) and amines (2947 and 2974 cm −1 ). They were very similar to the FTIR spectra recorded for structurally related substances: etonitazene and isotonitazene [14].…”

Section: Uv-vis and Ftir Spectroscopiessupporting

confidence: 79%

“…8. Some of observed ions (m/z 72, 100, 107, 135) was also recorded in case of isotonitazene [14] and etonitazene [34].…”

Section: Lc-ms/ms and Gc-ms/ms Analysesmentioning

confidence: 73%

“…It is worth emphasizing that the evidence material analyzed in our laboratory was of high purity, which may be considered as a specially dangerous. Interestingly, the authors of the paper regarding another benzimidazole opioid, isotonitazene, also noticed that the compound they described was sold undiluted [14].…”

Section: Discussionmentioning

confidence: 99%

“…Recent months have, however, brought a new trend that can be attributed to the legislative changes introduced in China [12] in May 2019. The use of non-fentanyl synthetic opioids [13], including benzimidazole derivatives [14,15], has started to appear on the European and American markets.…”

Section: Introductionmentioning

confidence: 99%

“…However, this situation has recently changed. In 2019, a paper was published on the detection of isotonitazene (2) on the drug market in Belgium [14], and poisoning cases associated with its use in Canada and the USA were reported [15]. The described cases allow to expect a dynamic increase in the number of this type of NPS on the drug market in the coming months.…”

Section: Introductionmentioning

confidence: 99%

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Etazene (N,N-diethyl-2-{[(4-ethoxyphenyl)methyl]-1H-benzimidazol-1-yl}-ethan-1-amine (dihydrochloride)): a novel benzimidazole opioid NPS identified in seized material: crystal structure and spectroscopic characterization

et al. 2020

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Purpose The aim of the study was to present the spectroscopic characteristics and crystal structure of the etazene—a benzimidazole opioid, which appeared on the illegal drug market in Poland in the last weeks. Methods The title compound was analyzed by X-ray crystallography as well as gas and liquid chromatography combined with mass spectrometry. Spectroscopic techniques have also been used, such as nuclear magnetic resonance, infrared and ultraviolet-visible spectroscopies. Results We presented the identification and the broad chemical characterization of etazene, a synthetic opioid that has recently been introduced on the illegal drug market. Conclusions In this paper, we described single-crystal X-ray, chromatographic and spectroscopic characterization of a synthetic opioid that emerged on the new psychoactive substance (NPS) market in Poland. To the best of our knowledge, this is the first full characterization of etazene. Analytical data presented in the work can be helpful in identification and detection of the NPS in forensic and clinical laboratories.

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Section: Uv-vis and Ftir Spectroscopiessupporting

confidence: 79%

“…8. Some of observed ions (m/z 72, 100, 107, 135) was also recorded in case of isotonitazene [14] and etonitazene [34].…”

Section: Lc-ms/ms and Gc-ms/ms Analysesmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Etazene (N,N-diethyl-2-{[(4-ethoxyphenyl)methyl]-1H-benzimidazol-1-yl}-ethan-1-amine (dihydrochloride)): a novel benzimidazole opioid NPS identified in seized material: crystal structure and spectroscopic characterization

et al. 2020

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Covalent and Visible‐Light Photoswitchable Derivatives of the Potent Synthetic Opioid Isotonitazene and Other Nitazenes

Lahmy,

Hübner,

Gmeiner

et al. 2024

ChemPhotoChem

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Isotonitazene belongs to a potent class of m‐opioid receptor (µOR) ligands, known as nitazenes. The lack of knowledge surrounding this agonist and others in its class has sparked thorough re‐investigations. To aid in these investigations, the purportedly covalent yet underexplored nitazene BIT was biochemically re‐evaluated in this work, along with a newly synthesized analogue, Iso‐BIT. Moreover, in the pursuit of understanding the mechanism, function, and interactions of µOR, this study involved developing photoswitchable derivatives of nitazene as potential probe molecules. Converting known ligands into azo‐containing photoswitchable derivatives offers the opportunity to modulate ligand structure with light, allowing for photocontrol of compound activity. While photocontrol of µOR activity could not be entirely achieved, photophysical evaluation of these arylazobenzimidazole derivatives revealed a novel photoswitch scaffold that responds to visible light. Furthermore, azo‐containing 2e and 3e emerged as promising nitazene derivatives that were able to form an exceptionally high fraction of covalent‐ligand receptor complexes with wild‐type µOR at physiological pH.

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Finding the proverbial needle: Non‐targeted screening of synthetic opioids in equine plasma

Klingberg

Cawley

Shimmon

et al. 2020

Drug Testing and Analysis

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Synthetic opioids are a class of compounds that are of particular concern due to their high potency and potential health impacts. With the relentless emergence of new synthetic opioid derivatives, non-targeted screening strategies are required that do not rely on the use of library spectra or reference materials. In this study, product ion searching, and Kendrick mass defect analysis were investigated for non-targeted screening of synthetic opioids. The estimated screening cut-offs for these techniques ranged between 0.05 and 0.1 ng/mL. These techniques were designed to not be reliant on a particular vendor's software, meaning that they can be applied to existing drug screening protocols, without requiring the development and validation of new analytical procedures. The efficacy of the developed techniques was tested through blind trials, with spiked samples inserted amongst authentic plasma samples, which demonstrated the usefulness of these methods for high-throughput screening. The use of a non-targeted screening workflow that contains complementary techniques can increase the likelihood of detecting compounds of interest within a sample, as well as the confidence in detections that are made.

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

Cited by 78 publications

References 25 publications

Etazene (N,N-diethyl-2-{[(4-ethoxyphenyl)methyl]-1H-benzimidazol-1-yl}-ethan-1-amine (dihydrochloride)): a novel benzimidazole opioid NPS identified in seized material: crystal structure and spectroscopic characterization

Etazene (N,N-diethyl-2-{[(4-ethoxyphenyl)methyl]-1H-benzimidazol-1-yl}-ethan-1-amine (dihydrochloride)): a novel benzimidazole opioid NPS identified in seized material: crystal structure and spectroscopic characterization

Covalent and Visible‐Light Photoswitchable Derivatives of the Potent Synthetic Opioid Isotonitazene and Other Nitazenes

Finding the proverbial needle: Non‐targeted screening of synthetic opioids in equine plasma

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