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Home > Synthesis, characterization and monoamine transporter activity of the new psychoactive substance mexedrone and its N-methoxy positional isomer, N-methoxymephedrone.

McLaughlin, Gavin and Morris, Noreen and Kavanagh, Pierce V and Power, John D and Dowling, Geraldine and Twamley, Brendan and O'Brien, John and Talbot, Brian and Walther, Donna and Partilla, John S and Baumann, Michael H and Brandt, Simon D (2017) Synthesis, characterization and monoamine transporter activity of the new psychoactive substance mexedrone and its N-methoxy positional isomer, N-methoxymephedrone. Drug Testing and Analysis, 9, (3), pp. 358-368.

External website: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC53365...

3-Methoxy-2-(methylamino)-1-(4-methylphenyl)propan-1-one (mexedrone) appeared in 2015 and was advertised by UK Internet retailers as a non-controlled mephedrone derivative (2-(methylamino)-1-(4-methylphenyl)propan-1-one), which was of particular interest to countries who operate generic drugs legislation. This study describes the synthesis and analytical characterization of mexedrone and the differentiation from its isomer, N-methoxymephedrone, which was predicted to be a suitable candidate before the identity of mexedrone was revealed. A full analytical characterization is described using various chromatographic, spectroscopic and mass spectrometric platforms and X-ray crystal structure analysis. The analytical data obtained for a vendor sample were consistent with the synthesized mexedrone reference standard and analytical differentiation between the mexedrone and N-methoxymephedrone positional isomers was achieved. Furthermore, α-chloromethylmephedrone was identified as a by-product during mexedrone synthesis. All three substances were also studied for their uptake and releasing properties at dopamine transporters (DAT), norepinephrine transporters (NET) and serotonin transporters (SERT) using in vitro monoamine transporter assays in rat brain synaptosomes and compared to mephedrone. Mexedrone was a weak non-selective uptake blocker with IC values in the low μM range. It was also devoid of releasing activity at DAT and NET but displayed weak releasing activity at SERT (EC  = 2.5 μM). The isomer N-methoxymephedrone was found to be a weak uptake blocker at DAT, NET and SERT, as well as a fully efficacious substrate-type releasing agent across all three transporters with EC values in the low micromolar range. The synthesis by-product α-chloromethylmephedrone was inactive in all assays. Copyright © 2016 John Wiley & Sons, Ltd.


Item Type
Article
Publication Type
Irish-related, International, Open Access, Article
Drug Type
New psychoactive substance
Intervention Type
Screening / Assessment
Date
2017
Page Range
pp. 358-368
Publisher
John Wiley & Sons, Ltd
Volume
9
Number
3
EndNote

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