Synthesis, characterization and monoamine transporter activity of the new psychoactive substance mexedrone and its N‐methoxy positional isomer, N‐methoxymephedrone
Gavin McLaughlin, Noreen Morris, Pierce V. Kavanagh, John D. Power, Geraldine Dowling, Brendan Twamley, John E. O’Brien, Brian Talbot, Donna Walther, John S. Partilla, Michael H. Baumann, Simon D. Brandt
Drug Testing and Analysis August 15, 2016 DOI: 10.1002/dta.2053 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro study Peer reviewed |
|---|---|
| Population | Rat brain synaptosomes |
| Intervention | Mexedrone |
| Topics | Serotonin 5-MeO-DMT |
| Keywords | Mephedrone Monoamine neurotransmitter Norepinephrine transporter Serotonin transporter Dopamine transporter Stereochemistry Pharmacology Biochemistry Drug Receptor |
| Citations | 23 |
| Key points | Mexedrone was a weak non-selective uptake blocker at dopamine, norepinephrine, and serotonin transporters and showed weak releasing activity only at serotonin transporters. |
Abstract
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 50 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 50 = 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 50 values in the low micromolar range. The synthesis by‐product α‐chloromethylmephedrone was inactive in all assays. Copyright © 2016 John Wiley & Sons, Ltd.
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| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
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| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 2
Cites 6
- New psychoactive substances as adulterants of controlled drugs. A worrying phenomenon? Drug Testing and Analysis 2014
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- Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats British Journal of Pharmacology May 26, 2011
- Drug testing in Europe: monitoring results of the Trans European Drug Information (TEDI) project. Drug Testing and Analysis February 2017
- The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue. Neuropsychopharmacology December 14, 2011
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