Synthesis, characterization, and monoamine transporter activity of the new psychoactive substance 3′,4′‐methylenedioxy‐4‐methylaminorex (MDMAR)
Gavin McLaughlin, Noreen Morris, Pierce V. Kavanagh, John D. Power, Brendan Twamley, John E. O’Brien, Brian Talbot, Geraldine Dowling, Olivia Mahony, Simon D. Brandt, Julian Patrick, Roland Archer, John S. Partilla, Michael H. Baumann
Drug Testing and Analysis October 20, 2014 DOI: 10.1002/dta.1732 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Laboratory study Peer reviewed |
|---|---|
| Population | Rat brain tissue |
| Topics | MDMA Serotonin |
| Keywords | Monoamine neurotransmitter Methylenedioxy Dopamine Norepinephrine transporter Formic acid Stereochemistry Pharmacology Chromatography Biochemistry Organic chemistry Receptor |
| Citations | 18 |
| Key points | cis-MDMAR, trans-MDMAR, cis-4,4'-DMAR, and trans-4,4'-DMAR were more potent than MDMA in releasing dopamine and norepinephrine at the DAT and NET in rat brain tissue. |
Abstract
The recent occurrence of deaths associated with the psychostimulant cis-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 cis- and trans-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 cis-isomer (90%). Exposure of the cis-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 trans-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 cis- and trans-4,4'-DMAR, were assessed under identical conditions. cis-MDMAR, trans-MDMAR, cis-4,4'-DMAR and trans-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 cis-4,4'-DMAR, cis-MDMAR and trans-MDMAR were fully efficacious releasing agents at the serotonin transporter (SERT), trans-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.
Comparable studies
Other experimental studies on MDMA, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin | 2000 | Experimental study | |
| Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Rat brain | 1988 | Experimental study | |
| The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Human platelet plasma membrane vesicles and bovine adrenal chromaffin granule membrane... | 1992 | Laboratory study | |
| Oxytocin-dependent reopening of a social reward learning critical period with MDMA | 2019 | Experimental study | |
| Effects of certain hallucinogenic amphetamine analogs on the release of [3H]-serotonin from rat brain synaptosomes Rat whole brain synaptosomes | 1982 | Experimental study |
Citations in the library
Cited by 6
- Designer drugs: mechanism of action and adverse effects Archives of Toxicology April 1, 2020
- The psychostimulant (±)-cis-4,4′-dimethylaminorex (4,4′-DMAR) interacts with human plasmalemmal and vesicular monoamine transporters Neuropharmacology June 23, 2018
- 4,4′‐Dimethylaminorex (“4,4′‐DMAR”; “Serotoni”) misuse: A Web‐based study Human Psychopharmacology: Clinical and Experimental May 1, 2017
- DARK Classics in Chemical Neuroscience: Aminorex Analogues ACS Chemical Neuroscience September 30, 2018
- The psychoactive aminoalkylbenzofuran derivatives, 5-APB and 6-APB, mimic the effects of 3,4-methylenedioxyamphetamine (MDA) on monoamine transmission in male rats. Psychopharmacology December 2020
and 1 more in the library
Cites 5
- Clinical toxicology of newer recreational drugs Clinical Toxicology October 1, 2011
- 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings Psychopharmacology March 15, 2006
- The new drug phenomenon Drug Testing and Analysis July 1, 2014
- Characterization of a novel and potentially lethal designer drug (±)‐cis‐para‐methyl‐4‐methylaminorex (4,4'‐DMAR, or ‘Serotoni’) Drug Testing and Analysis May 19, 2014
- The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue. Neuropsychopharmacology December 14, 2011