PMID- 24560859
OWN - NLM
STAT- MEDLINE
DCOM- 20140602
LR  - 20191210
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 101
IP  - 1-2
DP  - 2014 Apr 17
TI  - Elucidating the neurotoxic effects of MDMA and its analogs.
PG  - 37-42
LID - S0024-3205(14)00252-5 [pii]
LID - 10.1016/j.lfs.2014.02.010 [doi]
AB  - AIMS: There is a rapid increase in the use of methylenedioxymethamphetamine 
      (MDMA) and its structural congeners/analogs globally. MDMA and MDMA-analogs have 
      been synthesized illegally in furtive dwellings and are abused due to its 
      addictive potential. Furthermore, MDMA and MDMA-analogs have shown to have 
      induced several adverse effects. Hence, understanding the mechanisms mediating 
      this neurotoxic insult of MDMA-analogs is of immense importance for the public 
      health in the world. MAIN METHODS: We synthesized and investigated the neurotoxic 
      effects of MDMA and its analogs [4-methylenedioxyamphetamine (MDA), 2, 
      6-methylenedioxyamphetamine (MDMA), and N-ethyl-3, 4-methylenedioxyamphetamine 
      (MDEA)]. The stimulatory or the dopaminergic agonist effects of MDMA and 
      MDMA-analogs were elucidated using the established 6-hydroxydopamine lesioned 
      animal model. Additionally, we also investigated the neurotoxic mechanisms of 
      MDMA and MDMA-analogs on mitochondrial complex-I activity and reactive oxygen 
      species generation. KEY FINDINGS: MDMA and MDMA-analogs exhibited stimulatory 
      activity as compared to amphetamines and also induced several behavioral changes 
      in the rodents. MDMA and MDMA-analogs enhanced the reactive oxygen generation and 
      inhibited mitochondrial complex-I activity which can lead to neurodegeneration. 
      Hence the mechanism of neurotoxicity, MDMA and MDMA-analogs can enhance the 
      release of monoamines, alter the monoaminergic neurotransmission, and augment 
      oxidative stress and mitochondrial abnormalities leading to neurotoxicity. 
      SIGNIFICANCE: Thus, our study will help in developing effective pharmacological 
      and therapeutic approaches for the treatment of MDMA and MDMA-analog abuse.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Karuppagounder, Senthilkumar S
AU  - Karuppagounder SS
AD  - Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, 
      Auburn, AL, USA.
FAU - Bhattacharya, Dwipayan
AU  - Bhattacharya D
AD  - Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, 
      Auburn, AL, USA.
FAU - Ahuja, Manuj
AU  - Ahuja M
AD  - Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, 
      Auburn, AL, USA.
FAU - Suppiramaniam, Vishnu
AU  - Suppiramaniam V
AD  - Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, 
      Auburn, AL, USA.
FAU - Deruiter, Jack
AU  - Deruiter J
AD  - Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, 
      Auburn, AL, USA.
FAU - Clark, Randall
AU  - Clark R
AD  - Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, 
      Auburn, AL, USA.
FAU - Dhanasekaran, Muralikrishnan
AU  - Dhanasekaran M
AD  - Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, 
      Auburn, AL, USA. Electronic address: dhanamu@auburn.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140219
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Dopamine Agonists)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 8HW4YBZ748 (Oxidopamine)
RN  - EC 7.1.1.2 (Electron Transport Complex I)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/*drug effects
MH  - Brain/drug effects/metabolism
MH  - Dopamine Agonists/*toxicity
MH  - Electron Transport Complex I/*metabolism
MH  - Male
MH  - Mitochondrial Proteins/metabolism
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*analogs & derivatives/*toxicity
MH  - Oxidopamine
MH  - Rats
MH  - Reactive Oxygen Species/*metabolism
OTO - NOTNLM
OT  - Drugs of abuse
OT  - MDMA & analogs
OT  - Mitochondrial dysfunction
OT  - Neurotoxicity
OT  - Oxidative stress
EDAT- 2014/02/25 06:00
MHDA- 2014/06/03 06:00
CRDT- 2014/02/25 06:00
PHST- 2013/08/30 00:00 [received]
PHST- 2014/01/21 00:00 [revised]
PHST- 2014/02/08 00:00 [accepted]
PHST- 2014/02/25 06:00 [entrez]
PHST- 2014/02/25 06:00 [pubmed]
PHST- 2014/06/03 06:00 [medline]
AID - S0024-3205(14)00252-5 [pii]
AID - 10.1016/j.lfs.2014.02.010 [doi]
PST - ppublish
SO  - Life Sci. 2014 Apr 17;101(1-2):37-42. doi: 10.1016/j.lfs.2014.02.010. Epub 2014 
      Feb 19.