PMID- 25771452
OWN - NLM
STAT- MEDLINE
DCOM- 20160209
LR  - 20150410
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 755
DP  - 2015 May 15
TI  - The profile of mephedrone on human monoamine transporters differs from 
      3,4-methylenedioxymethamphetamine primarily by lower potency at the vesicular 
      monoamine transporter.
PG  - 119-26
LID - S0014-2999(15)00171-5 [pii]
LID - 10.1016/j.ejphar.2015.03.004 [doi]
AB  - Mephedrone (4-methylmethcathinone, MMC) and 3,4-methylenedioxymethamphetamine 
      (MDMA) are constituents of popular party drugs with psychoactive effects. 
      Structurally they are amphetamine-like substances with monoamine neurotransmitter 
      enhancing actions. We therefore compared their effects on the human monoamine 
      transporters using human cell lines stably expressing the human noradrenaline, 
      dopamine and serotonin transporter (NET, DAT and SERT); preparations of synaptic 
      vesicles from human striatum in uptake experiments; and a superfusion system 
      where releasing effects can be reliably measured. MMC and MDMA were equally 
      potent in inhibiting noradrenaline uptake at NET, with IC50 values of 1.9 and 2.1 
      microM, respectively. Compared to their NET inhibition potency, both drugs were 
      weaker uptake inhibitors at DAT and SERT, with MMC being more potent than MDMA at 
      DAT (IC50: 5.9 vs 12.6 microM) and less potent than MDMA at SERT (IC50: 19.3 vs 7.6 
      microM). MMC and MDMA both induced concentration-dependently 
      [(3)H]1-methyl-4-phenylpyridinium-release from NET-, DAT or SERT-expressing cells 
      which was clearly transporter-mediated release as demonstrated by the selective 
      inhibitory effects of nmolar to low micromolar concentrations of desipramine, GBR 
      12909 and fluoxetine, respectively. MMC and MDMA differed most in their 
      inhibition of [(3)H]dopamine uptake by synaptic vesicles from human striatum with 
      MDMA being 10-fold more potent than MMC (IC50: 20 vs 223 microM) and their ability to 
      release [(3)H]dopamine from human vesicular monoamine transporter expressing 
      SH-SY5Y neuroblastoma cells in which MDMA seems to have a stronger effect. Our 
      findings give a molecular explanation to the lower long-term neurotoxicity of MMC 
      compared to MDMA.
CI  - Copyright (c) 2015 Elsevier B.V. All rights reserved.
FAU - Pifl, Christian
AU  - Pifl C
AD  - Center for Brain Research, Medical University of Vienna, Spitalgasse 4, A-1090 
      Vienna, Austria. Electronic address: christian.pifl@meduniwien.ac.at.
FAU - Reither, Harald
AU  - Reither H
AD  - Center for Brain Research, Medical University of Vienna, Spitalgasse 4, A-1090 
      Vienna, Austria.
FAU - Hornykiewicz, Oleh
AU  - Hornykiewicz O
AD  - Center for Brain Research, Medical University of Vienna, Spitalgasse 4, A-1090 
      Vienna, Austria.
LA  - eng
PT  - Journal Article
DEP - 20150311
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (Norepinephrine Plasma Membrane Transport Proteins)
RN  - 0 (SLC18A2 protein, human)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Vesicular Monoamine Transport Proteins)
RN  - 44RAL3456C (Methamphetamine)
RN  - 8BA8T27317 (mephedrone)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Cell Line, Tumor
MH  - Dopamine Plasma Membrane Transport Proteins/*metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Methamphetamine/*analogs & derivatives/pharmacology
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Norepinephrine Plasma Membrane Transport Proteins/*metabolism
MH  - Serotonin Plasma Membrane Transport Proteins/*metabolism
MH  - Synaptic Vesicles/metabolism
MH  - Vesicular Monoamine Transport Proteins/*metabolism
OTO - NOTNLM
OT  - Amphetamines
OT  - Dopamine transporter
OT  - Noradrenaline transporter
OT  - Serotonin transporter
OT  - Synaptic vesicles
OT  - Vesicular monoamine transporter
EDAT- 2015/03/17 06:00
MHDA- 2016/02/10 06:00
CRDT- 2015/03/16 06:00
PHST- 2015/01/08 00:00 [received]
PHST- 2015/03/02 00:00 [revised]
PHST- 2015/03/04 00:00 [accepted]
PHST- 2015/03/16 06:00 [entrez]
PHST- 2015/03/17 06:00 [pubmed]
PHST- 2016/02/10 06:00 [medline]
AID - S0014-2999(15)00171-5 [pii]
AID - 10.1016/j.ejphar.2015.03.004 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2015 May 15;755:119-26. doi: 10.1016/j.ejphar.2015.03.004. Epub 
      2015 Mar 11.