PMID- 30776375
OWN - NLM
STAT- MEDLINE
DCOM- 20200106
LR  - 20221207
IS  - 1872-9711 (Electronic)
IS  - 0161-813X (Linking)
VI  - 72
DP  - 2019 May
TI  - Pharmacological characterization of the aminorex analogs 4-MAR, 4,4'-DMAR, and 
      3,4-DMAR.
PG  - 95-100
LID - S0161-813X(18)30523-0 [pii]
LID - 10.1016/j.neuro.2019.02.011 [doi]
AB  - 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      an amphetamine-like anorectic used in the 1960ies and withdrawn from the marked 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 (IC(50)<1 muM) 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 (K(i) values >2 muM). 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.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Rickli, Anna
AU  - Rickli A
AD  - Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, 
      University Hospital Basel and University of Basel, Basel, Switzerland.
FAU - Kolaczynska, Karolina
AU  - Kolaczynska K
AD  - Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, 
      University Hospital Basel and University of Basel, Basel, Switzerland.
FAU - Hoener, Marius C
AU  - Hoener MC
AD  - Neuroscience Research, pRED, Roche Innovation Center Basel, F. Hoffmann-La Roche 
      Ltd, Basel, Switzerland.
FAU - Liechti, Matthias E
AU  - Liechti ME
AD  - Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, 
      University Hospital Basel and University of Basel, Basel, Switzerland. Electronic 
      address: matthias.liechti@usb.ch.
LA  - eng
PT  - Journal Article
DEP - 20190215
PL  - Netherlands
TA  - Neurotoxicology
JT  - Neurotoxicology
JID - 7905589
RN  - 0 (Biogenic Monoamines)
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Norepinephrine Plasma Membrane Transport Proteins)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 2SH16612I9 (Aminorex)
SB  - IM
MH  - Aminorex/*analogs & derivatives/*pharmacology
MH  - Biogenic Monoamines/*metabolism
MH  - Central Nervous System Stimulants/*pharmacology
MH  - Dopamine Plasma Membrane Transport Proteins/antagonists & inhibitors/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Membrane Transport Proteins/*metabolism
MH  - Norepinephrine Plasma Membrane Transport Proteins/antagonists & 
      inhibitors/metabolism
MH  - Serotonin Plasma Membrane Transport Proteins/metabolism
MH  - Selective Serotonin Reuptake Inhibitors/administration & dosage
OTO - NOTNLM
OT  - 3,4-dimethylaminorex
OT  - 4,4'-dimethylaminorex
OT  - 4-methylaminorex
OT  - Aminorex
OT  - Monoamine
OT  - Novel psychoactive substance
EDAT- 2019/02/19 06:00
MHDA- 2020/01/07 06:00
CRDT- 2019/02/19 06:00
PHST- 2018/12/21 00:00 [received]
PHST- 2019/01/15 00:00 [revised]
PHST- 2019/02/14 00:00 [accepted]
PHST- 2019/02/19 06:00 [pubmed]
PHST- 2020/01/07 06:00 [medline]
PHST- 2019/02/19 06:00 [entrez]
AID - S0161-813X(18)30523-0 [pii]
AID - 10.1016/j.neuro.2019.02.011 [doi]
PST - ppublish
SO  - Neurotoxicology. 2019 May;72:95-100. doi: 10.1016/j.neuro.2019.02.011. Epub 2019 
      Feb 15.