Home > Characterization of a novel and potentially lethal designer drug (±)-cis-para-methyl-4-methylaminorex (4,4'-DMAR, or ‘Serotoni’)

Brandt, Simon D and Baumann, Michael H and Partilla, John S and Kavanagh, Pierce V and Power, John D and Talbot, Brian and Twamley, Brendan and Mahoney, Olivia and O'Brien, John and Elliott, Simon P and Archer, Roland P and Patrick, Julian and Singh, Kuldip and Dempster, Nicola M and Cosbey, Simon H (2014) Characterization of a novel and potentially lethal designer drug (±)-cis-para-methyl-4-methylaminorex (4,4'-DMAR, or ‘Serotoni’). Drug Testing and Analysis , 6 , (7-8) , pp. 684-695.

During the second half of 2013, a total of 26 deaths involving para-methyl-4-methylaminorex (4,4'-DMAR) were reported to the European Monitoring Centre for Drugs and Drug Addiction. While aminorex and 4-methylaminorex (4-MAR) are known psychostimulants, nothing is known about the comparatively new para-methyl analog. Analytical characterization of two independent samples obtained from online vendors confirmed the presence of the (±)-cis isomer that also appeared to be associated with at least 18 of the 26 deaths. Extensive characterizations included crystal structure analysis, single, tandem, and high-resolution mass spectrometry, liquid and gas chromatography, and nuclear magnetic resonance spectroscopy. For the work described here, both the (±)-cis and (±)-trans racemates were also synthesized, confirming that the differentiation between these two forms was straight-forward. Monoamine transporter activity was studied using rat brain synaptosomes which included the comparison with d-amphetamine, aminorex and (±)-cis-4-MAR. (±)-cis-4,4'-DMAR was a potent, efficacious substrate-type releaser at transporters for dopamine, norepinephrine and serotonin with EC50 values of 8.6 ± 1.1 nM (DAT), 26.9 ± 5.9 nM (NET) and 18.5 ± 2.8 nM (SERT), respectively. The potency of (±)-cis-4,4′-DMAR at DAT and NET rivalled that of other psychomotor stimulant drugs like d-amphetamine and aminorex. However, (±)-cis-4,4′-DMAR had much more potent actions at SERT and activity at SERT varied more than 100-fold across the four drugs. The potent releasing activity of (±)-cis-4,4′-DMAR at all three monoamine transporters predicts a potential for serious side-effects such as psychotic symptoms, agitation, hyperthermia and cardiovascular stimulation, especially after high-dose exposure or following combination with other psychostimulants.


Item Type:Article
Date:2014
Page Range:pp. 684-695
Volume:6
Number:7-8
EndNote:View
Accession Number:HRB (Not in collection)
Subjects:B Substances > New (novel) psychoactive substances
P Demography, epidemiology, and history > Population dynamics > Substance related mortality / death

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