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31.
Peter Blanckaert Annelies Cannaert Katleen Van Uytfanghe Fabian Hulpia Eric Deconinck Serge Van Calenbergh Christophe Stove 《Drug testing and analysis》2020,12(4):422-430
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. 相似文献
32.
Vugteveen Jorien de Bildt Annelies Hartman Catharina A. Reijneveld Sijmen A. Timmerman Marieke E. 《European child & adolescent psychiatry》2021,30(12):1983-1994
European Child & Adolescent Psychiatry - The Strengths and Difficulties Questionnaire (SDQ) is widely used, based on evidence of its value for screening. This evidence primarily regards the... 相似文献
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Gitta Bleeker Berthe L. van Eck-Smit Koos H. Zwinderman Rogier Versteeg Max M. van Noesel Boen L. Kam Gertjan J. Kaspers Annelies van Schie Susan G. Kreissman Gregory Yanik Barbara Hero Matthias Schmidt Geneviève Laureys Bieke Lambert Ingrid Øra Johannes H. Schulte Huib N. Caron Godelieve A. Tytgat 《European journal of nuclear medicine and molecular imaging》2015,42(2):222-230
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Carolina Noble Annelies Cannaert Kristian Linnet Christophe P. Stove 《Drug testing and analysis》2019,11(3):501-511
Synthetic cannabinoids (SCs) are the most chemically diverse group of new psychoactive substances. This group has been associated with several intoxications, many with fatal outcomes. Although advancements have been achieved in pharmacology, metabolism, and detection of these compounds in recent years, these aspects are still unresolved for many SCs. The aim of this study was to investigate the in vitro potency of 14 indole‐ and indazole‐based SCs by applying a stable CB1 or CB2 receptor activation assay and correlating the activity with their structure. The half‐maximal effective concentration (EC50) of 5‐chloropentyl, 5‐bromopentyl, and 5‐iodopentyl JWH‐122 analogs varied from 74.1 to 283.7 nM for CB1 and 7.05 to 23.4 nM for CB2, where the addition of a chlorine atom enhanced the potency at CB1 compared with the bromo and iodo analogs. AM‐2201 was the most active at CB1 within this naphthoylindole family, with an EC50 of 23.5 nM but with the lowest efficacy (Emax 98.8%). Within the indole‐3‐carboxamide derivatives, 5F‐MDMB‐PICA was the most active compound, with a CB1/CB2 EC50 of 3.26/0.87 nM and an Emax around three times higher than JWH‐018. ADB‐FUBINACA was the most potent tested SC overall, with a CB1/CB2 EC50 of 0.69/0.59 nM, and an Emax around 3‐fold higher than that for JWH‐018 at CB1. The data obtained in this study confirm how small differences in the structure of SCs might lead to large differences in their activity, especially at CB1, which may be correlated with differences in their toxic effects in humans. 相似文献
39.
Alexander Rodríguez-López Luisa N. Pimentel-Vera Angela J. Espejo-Mojica Annelies Van Hecke Petra Tiels Shunji Tomatsu Nico Callewaert Carlos J. Alméciga-Díaz 《Journal of pharmaceutical sciences》2019,108(8):2534-2541
Mucopolysaccharidosis IVA (MPS IVA or Morquio A syndrome) is a lysosomal storage disease caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), leading to lysosomal storage of keratan sulfate and chondroitin-6-sulfate. Currently, enzyme replacement therapy using an enzyme produced in CHO cells represents the main treatment option for MPS IVA patients. As an alternative, we reported the production of an active GALNS enzyme produced in the yeast Pichia pastoris (prGALNS), which showed internalization by cultured cells through a potential receptor-mediated process and similar post-translational processing as human enzyme. In this study, we further studied the therapeutic potential of prGALNS through the characterization of the N-glycosylation structure, in vitro cell uptake and keratan sulfate reduction, and in vivo biodistribution and generation of anti-prGALNS antibodies. Taken together, these results represent an important step in the development of a P. pastoris–based platform for production of a therapeutic GALNS for MPS IVA enzyme replacement therapy. 相似文献
40.
van Westreenen HL Visser A Tanis PJ Bemelman WA 《International journal of colorectal disease》2012,27(1):49-54