PMID- 22169943
OWN - NLM
STAT- MEDLINE
DCOM- 20120720
LR  - 20220318
IS  - 1740-634X (Electronic)
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 37
IP  - 5
DP  - 2012 Apr
TI  - The designer methcathinone analogs, mephedrone and methylone, are substrates for 
      monoamine transporters in brain tissue.
PG  - 1192-203
LID - 10.1038/npp.2011.304 [doi]
AB  - The nonmedical use of 'designer' cathinone analogs, such as 4-methylmethcathinone 
      (mephedrone) and 3,4-methylenedioxymethcathinone (methylone), is increasing 
      worldwide, yet little information is available regarding the mechanism of action 
      for these drugs. Here, we employed in vitro and in vivo methods to compare 
      neurobiological effects of mephedrone and methylone with those produced by the 
      structurally related compounds, 3,4-methylenedioxymethamphetamine (MDMA) and 
      methamphetamine. In vitro release assays using rat brain synaptosomes revealed 
      that mephedrone and methylone are nonselective substrates for plasma membrane 
      monoamine transporters, similar to MDMA in potency and selectivity. In vivo 
      microdialysis in rat nucleus accumbens showed that i.v. administration of 0.3 and 
      1.0 mg/kg of mephedrone or methylone produces dose-related increases in 
      extracellular dopamine and serotonin (5-HT), with the magnitude of effect on 5-HT 
      being greater. Both methcathinone analogs were weak motor stimulants when 
      compared with methamphetamine. Repeated administrations of mephedrone or 
      methylone (3.0 and 10.0 mg/kg, s.c., 3 doses) caused hyperthermia but no 
      long-term change in cortical or striatal amines, whereas similar treatment with 
      MDMA (2.5 and 7.5 mg/kg, s.c., 3 doses) evoked robust hyperthermia and persistent 
      depletion of cortical and striatal 5-HT. Our data demonstrate that designer 
      methcathinone analogs are substrates for monoamine transporters, with a profile 
      of transmitter-releasing activity comparable to MDMA. Dopaminergic effects of 
      mephedrone and methylone may contribute to their addictive potential, but this 
      hypothesis awaits confirmation. Given the widespread use of mephedrone and 
      methylone, determining the consequences of repeated drug exposure warrants 
      further study.
FAU - Baumann, Michael H
AU  - Baumann MH
AD  - Translational Pharmacology Section, Intramural Research Program, National 
      Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. 
      mbaumann@mail.nih.gov
FAU - Ayestas, Mario A Jr
AU  - Ayestas MA Jr
FAU - Partilla, John S
AU  - Partilla JS
FAU - Sink, Jacqueline R
AU  - Sink JR
FAU - Shulgin, Alexander T
AU  - Shulgin AT
FAU - Daley, Paul F
AU  - Daley PF
FAU - Brandt, Simon D
AU  - Brandt SD
FAU - Rothman, Richard B
AU  - Rothman RB
FAU - Ruoho, Arnold E
AU  - Ruoho AE
FAU - Cozzi, Nicholas V
AU  - Cozzi NV
LA  - eng
GR  - DA017675/DA/NIDA NIH HHS/United States
GR  - R21 DA017675/DA/NIDA NIH HHS/United States
GR  - DA027191/DA/NIDA NIH HHS/United States
GR  - ImNIH/Intramural NIH HHS/United States
GR  - R21 DA027191/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20111214
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (Hallucinogens)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Norepinephrine Plasma Membrane Transport Proteins)
RN  - 10028-17-8 (Tritium)
RN  - 333DO1RDJY (Serotonin)
RN  - 44RAL3456C (Methamphetamine)
RN  - 8BA8T27317 (mephedrone)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - L4I4B1R01F (methylone)
RN  - R865A5OY8J (1-Methyl-4-phenylpyridinium)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - 1-Methyl-4-phenylpyridinium/pharmacokinetics
MH  - Analysis of Variance
MH  - Animals
MH  - Chromatography, High Pressure Liquid
MH  - Dopamine/metabolism
MH  - Dopamine Plasma Membrane Transport Proteins/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Electrochemistry
MH  - Hallucinogens/pharmacology
MH  - In Vitro Techniques
MH  - Locomotion/drug effects
MH  - Male
MH  - *Membrane Transport Proteins
MH  - Methamphetamine/*analogs & derivatives/chemistry/pharmacology
MH  - Microdialysis/methods
MH  - N-Methyl-3,4-methylenedioxyamphetamine/pharmacology
MH  - Norepinephrine Plasma Membrane Transport Proteins/metabolism
MH  - Nucleus Accumbens/*drug effects/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serotonin/metabolism/pharmacokinetics
MH  - Synaptosomes/drug effects
MH  - Time Factors
MH  - Tritium/pharmacokinetics
PMC - PMC3306880
EDAT- 2011/12/16 06:00
MHDA- 2012/07/21 06:00
PMCR- 2013/04/01
CRDT- 2011/12/16 06:00
PHST- 2011/12/16 06:00 [entrez]
PHST- 2011/12/16 06:00 [pubmed]
PHST- 2012/07/21 06:00 [medline]
PHST- 2013/04/01 00:00 [pmc-release]
AID - npp2011304 [pii]
AID - 10.1038/npp.2011.304 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2012 Apr;37(5):1192-203. doi: 10.1038/npp.2011.304. Epub 
      2011 Dec 14.