Über Benzimidazolderivate mit starker analgetischer Wirkung

Gross, F.; Turrian, H

doi:10.1007/bf02161117

Cited by 46 publications

(32 citation statements)

References 2 publications

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“…Of these, the para-ethoxy substituent in etonitazene (6) yields the highest potency in both assays, followed by -isopropoxy, -propoxy, -methoxy, and -butoxy. Interestingly, this ranking matches that found in animal studies, where these compounds were compared with morphine 13,18 (S1). In terms of efficacy, the Emax values of isoto-, meto-, proto-, and butonitazene were roughly similar, while etonitazene remained the most efficacious compound.…”

Section: Resultssupporting

confidence: 82%

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

Vandeputte

Uytfanghe

Layle

et al. 2021

ACS Chem. Neurosci.

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Section: Resultssupporting

confidence: 82%

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

Vandeputte

Uytfanghe

Layle

et al. 2021

ACS Chem. Neurosci.

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“…However, although new in recreational North American drug supplies, the drug itself is not "newly discovered" as its pharmacology was described in pharmaceutical patents dating back to the 1950s and 1960s together with a closely related analogue: etonitazene (Figure 1). [5][6][7][8] A report documents the powerful analgesic effects of metonitazene from human clinical studies. 9 Metonitazene (EC 50 8.14 nM) is a potent synthetic opioid, albeit less potent than etonitazene (EC 50 0.661 nM), with purported potency similar to fentanyl (EC 50 14.4 nM) based on in vitro studies.…”

Section: Metonitazenementioning

confidence: 99%

Metonitazene in the United States—Forensic toxicology assessment of a potent new synthetic opioid using liquid chromatography mass spectrometry

Krotulski

Papsun²,

Walton

et al. 2021

Drug Testing and Analysis

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Metonitazene is considered a new psychoactive substance (NPS) and emerging potent synthetic opioid, causing increased public health concern beginning in 2020. Metonitazene joins a growing list of new synthetic opioids (NSOs) contributing to deaths among people who use drugs in the United States and other parts of the world. Metonitazene (a 2‐benzylbenzimidazole analogue) first appeared in mid‐2020 in the recreational drug supply and subsequently began proliferating in death investigation casework towards the end of 2020. Screening and metabolite discovery were performed by liquid chromatography quadrupole time‐of‐flight mass spectrometry. Quantitative confirmation was performed by liquid chromatography tandem quadrupole mass spectrometry. Metonitazene was confirmed in 20 authentic forensic postmortem cases with an average concentration in blood at 6.3 ± 7.5 ng/ml (median: 3.8 ng/ml, range: 0.5–33 ng/ml, n = 18) and in urine at 15 ± 13 ng/ml (median: 11 ng/ml, range: 0.6–46 ng/ml, n = 14). Metonitazene was the only opioid identified in 30% of cases but was also found in combination with fentanyl (55%) and NPS benzodiazepines, opioids, and hallucinogens (45%). Medical examiners included metonitazene as a drug responsible for the cause of death, and the manner of death was always ruled to be an accident. The metabolism of metonitazene was found to be similar to that of isotonitazene, a closely related analogue. Toxicology laboratories and death investigators should ensure that metonitazene is included in forensic testing protocols, all while remaining vigilant for subsequent NSOs to emerge.

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“…In this paper we report on the identification and full characterization of a novel NPS opioid sourced online: isotonitazene ( N , N ‐diethyl‐2‐[5‐nitro‐2‐({4‐[(propan‐2‐yl)oxy]phenyl}methyl)‐1H‐benzimidazol‐1‐yl]ethan‐1‐amine; chemical structure can be found in Figure ), which is the first detected member of a new benzimidazole class of NPS opioids. This type of compound is not new – the synthesis of benzimidazole derivatives with analgesic activity was first reported in 1957 . Since then, other, simplified synthesis pathways have been described, including a relatively simple one‐pot, three‐component synthesis at high yield .…”

Section: Introductionmentioning

confidence: 99%

“…This type of compound is not newthe synthesis of benzimidazole derivatives with analgesic activity was first reported in 1957. 15,16 Since then, other, simplified synthesis pathways have been described, including a relatively simple one-pot, three-component synthesis at high yield. 17 Although several derivatives were patented, [18][19][20][21] no clinically approved therapeutics have made it to the market.…”

Section: Introductionmentioning

confidence: 99%

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

Blanckaert

Cannaert

Uytfanghe

et al. 2020

Drug Testing and Analysis

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This 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.

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Über Benzimidazolderivate mit starker analgetischer Wirkung

Cited by 46 publications

References 2 publications

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

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

Metonitazene in the United States—Forensic toxicology assessment of a potent new synthetic opioid using liquid chromatography mass spectrometry

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

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