PMID- 21562283
OWN - NLM
STAT- MEDLINE
DCOM- 20110725
LR  - 20211020
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 31
IP  - 19
DP  - 2011 May 11
TI  - Characterization of 3,4-methylenedioxymethamphetamine (MDMA) enantiomers in vitro 
      and in the MPTP-lesioned primate: R-MDMA reduces severity of dyskinesia, whereas 
      S-MDMA extends duration of ON-time.
PG  - 7190-8
LID - 10.1523/JNEUROSCI.1171-11.2011 [doi]
AB  - l-3,4-dihydroxyphenylalanine (l-DOPA) is the most effective treatment for 
      Parkinson's disease, but long-term l-DOPA administration is marred by the 
      emergence of motor complications, namely, dyskinesia and a shortening of 
      antiparkinsonian benefit (wearing-OFF). 3,4-methylenedioxymethamphetamine (MDMA) 
      is unique in that it exerts antidyskinetic effects and may enhance 
      antiparkinsonian actions of l-DOPA. MDMA is composed of two enantiomers with 
      different pharmacological profiles; here, we describe a novel enantiospecific 
      synthesis of the two enantiomers and expand on the previous characterization of 
      their pharmacology. R-MDMA (rectus-MDMA) is relatively selective for 5-HT(2A) 
      receptors, whereas S-MDMA (sinister-MDMA) inhibits both serotonin (SERT) and 
      dopamine transporters (DAT; SERT/DAT ratio of 10 to 1). R- or S-MDMA (1, 3, and 
      10 mg/kg, s.c.) was administered in combination with l-DOPA (15 mg/kg, s.c.) to 
      six female common marmosets (Callithrix jacchus) rendered parkinsonian by MPTP 
      (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) administration. Motor disability, 
      including parkinsonism and dyskinesia, and duration of antiparkinsonian benefit 
      (ON-time) were evaluated. After the administration of R-MDMA (3 and 10 mg/kg), 
      the severity of peak-dose dyskinesia was decreased (by 33 and 46%, respectively; 
      p < 0.05); although total ON-time was unchanged (approximately 220 min), the 
      duration of ON-time with disabling dyskinesia was decreased by 90 min when 
      compared to l-DOPA alone (69% reduction; p < 0.05). S-MDMA (1 mg/kg) increased 
      the total ON-time by 88 min compared to l-DOPA alone (34% increase; p < 0.05), 
      though dyskinesia were exacerbated. These data suggest that racemic MDMA exerts 
      simultaneous effects, reducing dyskinesia and extending ON-time, by 5-HT(2A) 
      antagonism and SERT-selective mixed monoamine uptake inhibition, which arise from 
      its R and S enantiomers, respectively.
FAU - Huot, Philippe
AU  - Huot P
AD  - Toronto Western Research Institute, Toronto Western Hospital, University Health 
      Network, Toronto, Ontario M5T 2S8, Canada.
FAU - Johnston, Tom H
AU  - Johnston TH
FAU - Lewis, Katie D
AU  - Lewis KD
FAU - Koprich, James B
AU  - Koprich JB
FAU - Reyes, M Gabriela
AU  - Reyes MG
FAU - Fox, Susan H
AU  - Fox SH
FAU - Piggott, Matthew J
AU  - Piggott MJ
FAU - Brotchie, Jonathan M
AU  - Brotchie JM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Antiparkinson Agents)
RN  - 46627O600J (Levodopa)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Antiparkinson Agents/therapeutic use/*toxicity
MH  - Behavior, Animal/drug effects
MH  - Brain/*drug effects
MH  - Callithrix
MH  - Dyskinesia, Drug-Induced/*drug therapy/physiopathology
MH  - Female
MH  - Levodopa/therapeutic use/*toxicity
MH  - MPTP Poisoning/drug therapy
MH  - Motor Activity/drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine/chemistry/*therapeutic use
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Severity of Illness Index
MH  - Stereoisomerism
PMC - PMC6703214
EDAT- 2011/05/13 06:00
MHDA- 2011/07/26 06:00
PMCR- 2011/11/11
CRDT- 2011/05/13 06:00
PHST- 2011/05/13 06:00 [entrez]
PHST- 2011/05/13 06:00 [pubmed]
PHST- 2011/07/26 06:00 [medline]
PHST- 2011/11/11 00:00 [pmc-release]
AID - 31/19/7190 [pii]
AID - 3694888 [pii]
AID - 10.1523/JNEUROSCI.1171-11.2011 [doi]
PST - ppublish
SO  - J Neurosci. 2011 May 11;31(19):7190-8. doi: 10.1523/JNEUROSCI.1171-11.2011.