Report on a novel emerging class of highly potent benzimidazole NPS opioids: Chemical and in vitro functional characterization of isotonitazene
Report on a novel emerging class of highly potent benzimidazole NPS opioids: Chemical and in vitro functional characterization of isotonitazene
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DOI：
10.1002/dta.2738
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发表时间：
2020-01-08
影响因子：
2.9
通讯作者：
Stove, Christophe
中科院分区：
文献类型：
--
作者：
Blanckaert, Peter;Cannaert, Annelies;Stove, Christophe
本文报道了异渗氮酮 (N,N-di乙基-2-[5-硝基-2-({4-[(丙-2-基)氧基]苯基}甲基)-1H-苯并咪唑-1-基]乙烷-1-胺) 的鉴定和完整化学表征，异渗氮酮是一种强效 NPS 阿片类药物，也是在线市场上第一个上市的苯并咪唑类化合物。有趣的是，这种化合物以结构类似物依托硝氮的名称出售。通过气相色谱质谱 (GC-MS) 和液相色谱飞行时间质谱 (LC-QTOF-MS) 鉴定异渗氮酮，后者鉴定出精确质量 m/z 值为 411.2398。所有色谱数据均表明存在单一的高纯度化合物。使用 H-1 和 C-13 NMR 光谱确认特定的苯并咪唑区域异构体，然后通过记录傅里叶变换 (FT-IR) 光谱完成化学表征。用于评估 mu-阿片受体 (MOR) 体外生物活性的活细胞报告测定表明，异渗氮酮具有高效价（EC50 为 11.1 nM）和功效（E-max 为氢吗啡酮的 180%），从而证实该物质是强阿片类药物。以前从未在粉末形式或生物液体中检测到异渗氮酮。异托氮嗪的高效力和功效，加上该化合物未经稀释出售，对任何打算使用这种粉末的人来说都构成迫在眉睫的危险。
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 H-1 and C-13 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 mu-opioid receptor (MOR) revealed that isotonitazene has a high potency (EC50 of 11.1 nM) and efficacy (E-max 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.