Synthesis, characterization, and monoamine transporter activity of the new psychoactive substance 3′, 4′‐methylenedioxy‐4‐methylaminorex (MDMAR). Issue 7 (20th October 2014)

• Record Type: Journal Article
• Authors: McLaughlin, Gavin; Morris, Noreen; Kavanagh, Pierce V.; Power, John D.; Twamley, Brendan; O'Brien, John; Talbot, Brian; Dowling, Geraldine; Mahony, Olivia; Brandt, Simon D.; Patrick, Julian; Archer, Roland P.; Partilla, John S.; Baumann, Michael H.
• Is Part Of: Drug testing and analysis. Volume 7:Issue 7(2015:Jul.)
• Page Start: 555
• Page End: 564
• Publication Date: 2014-10-20
• Subjects: Drugs -- Analysis -- Periodicals; Drug testing -- Periodicals; Chemistry, Forensic -- Periodicals; 615.1901
• DOI: 10.1002/dta.1732
• Languages: English
• ISSNs: 1942-7603

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The recent occurrence of deaths associated with the psychostimulant <italic>cis</italic>‐4, 4′‐dimethylaminorex (4, 4′‐DMAR) in Europe indicated the presence of a newly emerged psychoactive substance on the market. Subsequently, the existence of 3, 4‐methylenedioxy‐4‐methylaminorex (MDMAR) has come to the authors' attention and this study describes the synthesis of <italic>cis</italic>‐ and <italic>trans</italic>‐MDMAR followed by extensive characterization by chromatographic, spectroscopic, mass spectrometric platforms and crystal structure analysis. MDMAR obtained from an online vendor was subsequently identified as predominantly the <italic>cis</italic>‐isomer (90%). Exposure of the <italic>cis</italic>‐isomer to the mobile phase conditions (acetonitrile/water 1:1 with 0.1% formic acid) employed for high performance liquid chromatography analysis showed an artificially induced conversion to the <italic>trans</italic>‐isomer, which was not observed when characterized by gas chromatography. Monoamine release activities of both MDMAR isomers were compared with the non‐selective monoamine releasing agent (+)‐3, 4‐methylenedioxymethamphetamine (MDMA) as a standard reference compound. For additional comparison, both <italic>cis</italic>‐ and <italic>trans</italic>‐4, 4′‐DMAR, were assessed under identical conditions. <italic>cis</italic>‐MDMAR, <italic>trans</italic>‐MDMAR, <italic>cis</italic>‐4, 4′‐DMAR and <italic>trans</italic>‐4, 4′‐DMAR were more potent than MDMA in their ability to function as efficacious substrate‐type releasers at the dopamine (DAT) and norepinephrine (NET) transporters in rat brain tissue. While <italic>cis</italic>‐4, 4′‐DMAR, <italic>cis</italic>‐MDMAR and <italic>trans</italic>‐MDMAR were fully efficacious releasing agents at the serotonin transporter (SERT), <italic>trans</italic>‐4, 4′‐DMAR acted as a fully efficacious uptake blocker. Currently, little information is available about the presence of MDMAR on the market but the high potency of ring‐substituted methylaminorex analogues at all three monoamine transporters investigated here might be relevant when assessing the potential for serious side‐effects after high dose exposure. Copyright © 2014 John Wiley & Sons, Ltd.</p> </abstract>