PMID- 26721607
OWN - NLM
STAT- MEDLINE
DCOM- 20160530
LR  - 20160124
IS  - 1879-3169 (Electronic)
IS  - 0378-4274 (Linking)
VI  - 243
DP  - 2016 Jan 22
TI  - Inhibition potential of 3,4-methylenedioxymethamphetamine (MDMA) and its 
      metabolites on the in vitro monoamine oxidase (MAO)-catalyzed deamination of the 
      neurotransmitters serotonin and dopamine.
PG  - 48-55
LID - S0378-4274(15)30129-6 [pii]
LID - 10.1016/j.toxlet.2015.12.001 [doi]
AB  - Neurotoxicity of 3,4-methylenedioxymethamphetamine (MDMA) is still 
      controversially discussed. Formation of reactive oxygen species e.g. based on 
      elevated dopamine (DA) concentrations and DA quinone formation is discussed among 
      others. Inhibition potential of MDMA metabolites regarding neurotransmitter 
      degradation by catechol-O-methyltransferase and sulfotransferase was described 
      previously. Their influence on monoamine oxidase (MAO) - the major DA degradation 
      pathway-has not yet been studied in humans. Therefore the inhibition potential of 
      MDMA and its metabolites on the deamination of the neurotransmitters DA and 
      serotonin (5-HT) by MAO-A and B using recombinant human enzymes in vitro should 
      be investigated. In initial studies, MDMA and MDA showed relevant inhibition 
      (>30%) toward MAO A for 5-HT and DA. No relevant effects toward MAO B were 
      observed. Further investigation on MAO-A revealed MDMA as a competitive inhibitor 
      of 5-HT and DA deamination with Ki 24.5+/-7.1 muM and 18.6+/-4.3 muM respectively and 
      MDA as a mixed-type inhibitor with Ki 7.8+/-2.6 muM and 8.4+/-3.2 muM respectively. 
      Although prediction of in vivo relevance needs to be done with care, relevant 
      inhibitory effects at expected plasma concentrations after recreational MDMA 
      consumption seems unlikely based on the obtained data.
CI  - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved.
FAU - Steuer, Andrea E
AU  - Steuer AE
AD  - Department of Forensic Pharmacology & Toxicology, Institute of Forensic Medicine, 
      University of Zurich, Switzerland. Electronic address: andrea.steuer@irm.uzh.ch.
FAU - Boxler, Martina I
AU  - Boxler MI
AD  - Department of Forensic Pharmacology & Toxicology, Institute of Forensic Medicine, 
      University of Zurich, Switzerland.
FAU - Stock, Lorena
AU  - Stock L
AD  - Department of Forensic Pharmacology & Toxicology, Institute of Forensic Medicine, 
      University of Zurich, Switzerland.
FAU - Kraemer, Thomas
AU  - Kraemer T
AD  - Department of Forensic Pharmacology & Toxicology, Institute of Forensic Medicine, 
      University of Zurich, Switzerland.
LA  - eng
PT  - Journal Article
DEP - 20151222
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Monoamine Oxidase Inhibitors)
RN  - 0 (Neurotransmitter Agents)
RN  - 0 (Reactive Oxygen Species)
RN  - 333DO1RDJY (Serotonin)
RN  - 50673-96-6 (dopamine quinone)
RN  - EC 1.4.3.4 (Monoamine Oxidase)
RN  - EC 2.1.1.6 (Catechol O-Methyltransferase)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Catechol O-Methyltransferase/metabolism
MH  - Chromatography, Liquid
MH  - Deamination
MH  - Dopamine/*analogs & derivatives/metabolism
MH  - Humans
MH  - Inhibitory Concentration 50
MH  - Monoamine Oxidase/*metabolism
MH  - Monoamine Oxidase Inhibitors/blood/*toxicity
MH  - N-Methyl-3,4-methylenedioxyamphetamine/blood/*toxicity
MH  - Neurotransmitter Agents/metabolism
MH  - Reactive Oxygen Species
MH  - Serotonin/*metabolism
MH  - Tandem Mass Spectrometry
OTO - NOTNLM
OT  - In vitro
OT  - Inhibition
OT  - MAO
OT  - MDMA
OT  - Neurotransmitter
EDAT- 2016/01/02 06:00
MHDA- 2016/05/31 06:00
CRDT- 2016/01/02 06:00
PHST- 2015/10/05 00:00 [received]
PHST- 2015/12/08 00:00 [revised]
PHST- 2015/12/18 00:00 [accepted]
PHST- 2016/01/02 06:00 [entrez]
PHST- 2016/01/02 06:00 [pubmed]
PHST- 2016/05/31 06:00 [medline]
AID - S0378-4274(15)30129-6 [pii]
AID - 10.1016/j.toxlet.2015.12.001 [doi]
PST - ppublish
SO  - Toxicol Lett. 2016 Jan 22;243:48-55. doi: 10.1016/j.toxlet.2015.12.001. Epub 2015 
      Dec 22.