PMID- 22188379
OWN - NLM
STAT- MEDLINE
DCOM- 20121030
LR  - 20240418
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 166
IP  - 5
DP  - 2012 Jul
TI  - Lost in translation: preclinical studies on 3,4-methylenedioxymethamphetamine 
      provide information on mechanisms of action, but do not allow accurate prediction 
      of adverse events in humans.
PG  - 1523-36
LID - 10.1111/j.1476-5381.2011.01819.x [doi]
AB  - 3,4-Methylenedioxymethamphetamine (MDMA) induces both acute adverse effects and 
      long-term neurotoxic loss of brain 5-HT neurones in laboratory animals. However, 
      when choosing doses, most preclinical studies have paid little attention to the 
      pharmacokinetics of the drug in humans or animals. The recreational use of MDMA 
      and current clinical investigations of the drug for therapeutic purposes demand 
      better translational pharmacology to allow accurate risk assessment of its 
      ability to induce adverse events. Recent pharmacokinetic studies on MDMA in 
      animals and humans are reviewed and indicate that the risks following MDMA 
      ingestion should be re-evaluated. Acute behavioural and body temperature changes 
      result from rapid MDMA-induced monoamine release, whereas long-term neurotoxicity 
      is primarily caused by metabolites of the drug. Therefore acute physiological 
      changes in humans are fairly accurately mimicked in animals by appropriate 
      dosing, although allometric dosing calculations have little value. Long-term 
      changes require MDMA to be metabolized in a similar manner in experimental 
      animals and humans. However, the rate of metabolism of MDMA and its major 
      metabolites is slower in humans than rats or monkeys, potentially allowing 
      endogenous neuroprotective mechanisms to function in a species specific manner. 
      Furthermore acute hyperthermia in humans probably limits the chance of 
      recreational users ingesting sufficient MDMA to produce neurotoxicity, unlike in 
      the rat. MDMA also inhibits the major enzyme responsible for its metabolism in 
      humans thereby also assisting in preventing neurotoxicity. These observations 
      question whether MDMA alone produces long-term 5-HT neurotoxicity in human brain, 
      although when taken in combination with other recreational drugs it may induce 
      neurotoxicity.
CI  - (c) 2011 The Authors. British Journal of Pharmacology (c) 2011 The British 
      Pharmacological Society.
FAU - Green, A R
AU  - Green AR
AD  - School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham, 
      UK. richard.green@nottingham.ac.uk
FAU - King, M V
AU  - King MV
FAU - Shortall, S E
AU  - Shortall SE
FAU - Fone, K C F
AU  - Fone KC
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Blood Proteins)
RN  - 0 (Hallucinogens)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
CIN - Br J Pharmacol. 2012 Jul;166(5):1518-20; discussion 1521-2. PMID: 22404300
MH  - Animals
MH  - Blood Proteins/metabolism
MH  - Drug Evaluation, Preclinical
MH  - Hallucinogens/*adverse effects/blood/pharmacokinetics
MH  - Humans
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*adverse effects/blood/pharmacokinetics
MH  - Neurotoxicity Syndromes/*etiology/metabolism
MH  - Protein Binding
MH  - Species Specificity
PMC - PMC3419898
EDAT- 2011/12/23 06:00
MHDA- 2012/10/31 06:00
PMCR- 2013/07/01
CRDT- 2011/12/23 06:00
PHST- 2011/12/23 06:00 [entrez]
PHST- 2011/12/23 06:00 [pubmed]
PHST- 2012/10/31 06:00 [medline]
PHST- 2013/07/01 00:00 [pmc-release]
AID - 10.1111/j.1476-5381.2011.01819.x [doi]
PST - ppublish
SO  - Br J Pharmacol. 2012 Jul;166(5):1523-36. doi: 10.1111/j.1476-5381.2011.01819.x.