Structural characterization and pharmacological evaluation of the new synthetic cannabinoid CUMYL-PEGACLONE.

Autor: Angerer V; Institute of Forensic Medicine, Forensic Toxicology, Medical Center - University of Freiburg, Germany.; Hermann Staudinger Graduate School, University of Freiburg, Germany., Mogler L; Institute of Forensic Medicine, Forensic Toxicology, Medical Center - University of Freiburg, Germany.; Hermann Staudinger Graduate School, University of Freiburg, Germany., Steitz JP; Institute for Pharmaceutical Sciences, University of Freiburg, Germany., Bisel P; Institute for Pharmaceutical Sciences, University of Freiburg, Germany., Hess C; Institute of Forensic Medicine, Forensic Toxicology, University of Bonn, Germany., Schoeder CT; PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, Germany., Müller CE; PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, Germany., Huppertz LM; Institute of Forensic Medicine, Forensic Toxicology, Medical Center - University of Freiburg, Germany., Westphal F; State Bureau of Criminal Investigation Schleswig-Holstein, Kiel, Germany., Schäper J; State Bureau of Criminal Investigation Bavaria, München, Germany., Auwärter V; Institute of Forensic Medicine, Forensic Toxicology, Medical Center - University of Freiburg, Germany.
Jazyk: angličtina
Zdroj: Drug testing and analysis [Drug Test Anal] 2018 Mar; Vol. 10 (3), pp. 597-603. Date of Electronic Publication: 2017 Aug 09.
DOI: 10.1002/dta.2237
Abstrakt: The number of new psychoactive substances (NPS) that have emerged on the European market has been rapidly growing in recent years, with a particularly high number of new compounds from the group of synthetic cannabinoid receptor agonists. There have been various political efforts to control the trade and the use of NPS worldwide. In Germany, the Act to control the distribution of new psychoactive substances (NpSG) came into force in November 2016. In this new act, two groups of substances were defined, the group "cannabimimetics/synthetic cannabinoids" covering indole, indazole, and benzimidazole core structures, and a second group named "compounds derived from 2-phenethylamine." Shortly after, the first retailers of "herbal blends" promoted new products allegedly not violating the German NpSG. We describe the identification and structural elucidation of one of the first synthetic cannabinoids not being covered by the NpSG, 5-pentyl-2-(2-phenylpropan-2-yl)-2,5-dihydro-1H-pyrido[4,3-b]indol-1-one. For isolation of the substance a flash chromatography separation was applied. The structure elucidation was performed using gas chromatography-mass spectrometry (GC-MS), gas chromatography-solid state infrared spectroscopy (GC-sIR), liquid chromatography-electrospray ionization-quadrupole time of flight-mass spectrometry (LC-ESI-qToF-MS) and nuclear magnetic resonance (NMR) analysis. Additionally, binding affinity towards the cannabinoid receptors CB 1 and CB 2 and efficacy in a cAMP accumulation assay were measured, showing full agonistic activity and high potency at both receptors. The new compound bears a γ-carboline core structure circumventing the German NpSG and the generic definitions in other national laws. As a semi-systematic name for 2-cumyl-5-pentyl-gamma-carbolin-1-one CUMYL-PEGACLONE is suggested.
(Copyright © 2017 John Wiley & Sons, Ltd.)
Databáze: MEDLINE
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