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Pharmacological characterization of the aminorex analogs 4-MAR, 4,4'-DMAR, and 3,4-DMAR.
Journal article

Pharmacological characterization of the aminorex analogs 4-MAR, 4,4'-DMAR, and 3,4-DMAR.

  • Rickli A Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland.
  • Kolaczynska K Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland.
  • Hoener MC Neuroscience Research, pRED, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
  • Liechti ME Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland. Electronic address: matthias.liechti@usb.ch.
  • 2019-02-19
Published in:
  • Neurotoxicology. - 2019
3,4-dimethylaminorex
4,4′-dimethylaminorex
4-methylaminorex
Aminorex
Monoamine
Novel psychoactive substance
Aminorex
Biogenic Monoamines
Central Nervous System Stimulants
Dopamine Plasma Membrane Transport Proteins
HEK293 Cells
Humans
Membrane Transport Proteins
Norepinephrine Plasma Membrane Transport Proteins
Serotonin Plasma Membrane Transport Proteins
Serotonin Uptake Inhibitors
English 4,4'-Dimethylaminorex (4,4'-DMAR) is a novel psychoactive substance (NPS) that appeared on the illicit drug market in addition to the psychostimulant 4-methylaminorex (4-MAR). Both substances are methylated derivatives of aminorex, an amphetamine-like anorectic used in the 1960ies and withdrawn from the marked due to severe cardiovascular toxicity. The aim of the present study was to characterize the in vitro pharmacological profiles of 4-MAR, 4,4'-DMAR, and 3,4-dimethylaminorex (3,4-DMAR, direx). We assessed norepinephrine (NE), dopamine (DA), and serotonin (5-HT) transporter inhibition potencies and monoamine release in transporter-transfected human embryonic kidney (HEK) 293 cells. We also assessed monoamine receptor and transporter binding affinities. 4,4'-DMAR potently inhibited all monoamine transporters (IC50<1 μM) with greater potency than 3,4-methlyenedioxymethamphetaime (MDMA) and displayed a higher serotonergic over dopaminergic preference, relatively similar to MDMA (DA transporter / 5-HT transporter inhibition ratio of 0.4 and 0.08 for 4,4'-DMAR and MDMA, respectively). In contrast, 4-MAR preferentially inhibited the NE and DA transporter, exhibiting a pharmacological profile more similar to amphetamine. Both 4-MAR and 4,4'-DMAR were also substrate releasers at the DAT. 3,4-DMAR only weakly inhibited the NE transporter and showed no relevant activity at the DA and 5-HT transporter. Binding affinities of all three aminorex derivatives at various monoamine receptors were negligible (Ki values >2 μM). The in vitro pharmacological profiles indicate that 4,4'-DMAR has comparable psychoactive properties and serotonergic toxicity to MDMA and may be more potent. 4-MAR is a psychostimulant similar to amphetamine or methamphetamine. 3,4-DMAR likely has only weak psychostimulant properties.
Language
  • English
Open access status
closed
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Persistent URL
https://sonar.ch/global/documents/73250
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