PMID- 21871156
OWN - NLM
STAT- MEDLINE
DCOM- 20120112
LR  - 20211020
IS  - 1945-2403 (Electronic)
IS  - 0146-4760 (Print)
IS  - 0146-4760 (Linking)
VI  - 35
IP  - 7
DP  - 2011 Sep
TI  - (+/-)-3,4-methylenedioxymethamphetamine and metabolite disposition in plasma and 
      striatum of wild-type and multidrug resistance protein 1a knock-out mice.
PG  - 470-80
AB  - Mice lacking multidrug resistance protein 1a (mdr1a) are protected from 
      methylenedioxymethamphetamine (MDMA)-induced neurotoxicity, suggesting mdr1a 
      might play an important role in this phenomenon. We characterized MDMA 
      pharmacokinetics in murine plasma and brain to determine if mdr1a alters MDMA 
      distribution. Wild-type (mdr1a(+)/(+)) and mdr1a knock-out (mdr1a(-)/(-)) mice received 
      i.p. 10, 20 or 40 mg/kg MDMA. Plasma and brain specimens were collected 0.3-4 h 
      after MDMA, and striatum were dissected. MDMA and metabolites were quantified in 
      plasma and striatum by gas chromatography-mass spectrometry. MDMA maximum plasma 
      concentrations (C(max)) for both strains were 916- 1363, 1833-3546, and 5979-7948 
      mug/L, whereas brain C(max) were 6673-14,869, 23,428-29,433, and 52,735-66,525 
      mug/kg after 10, 20, or 40 mg/kg MDMA, respectively. MDMA and metabolite 
      striatum/plasma AUC ratios were similar in both strains, inconsistent with 
      observed MDMA neuroprotective effects in mdr1a(-)/(-) mice. Ratios of 
      methylenedioxyamphetamine (MDA) and 4-hydroxy-3-methoxymethamphetamine (HMMA) 
      AUCs exceeded 18% of MDMA's in plasma, suggesting substantial MDMA hepatic 
      metabolism in mice. MDMA, MDA, HMMA, and 4-hydroxy-3-methoxyamphetamine maximum 
      concentrations and AUCs exhibited nonlinear relationships during dose-escalation 
      studies, consistent with impaired enzymatic demethylenation. Nonlinear increases 
      in MDMA plasma and brain concentrations with increased MDMA dose may potentiate 
      MDMA effects and toxicity.
FAU - Scheidweiler, Karl B
AU  - Scheidweiler KB
AD  - Chemistry and Drug Metabolism Section, Intramural Research Program, National 
      Institute on Drug Abuse, National Institutes of Health, Biomedical Research 
      Center, 251 Bayview Boulevard, Baltimore, Maryland 21224, USA.
FAU - Ladenheim, Bruce
AU  - Ladenheim B
FAU - Barnes, Allan J
AU  - Barnes AJ
FAU - Cadet, Jean Lud
AU  - Cadet JL
FAU - Huestis, Marilyn A
AU  - Huestis MA
LA  - eng
GR  - Z99 DA999999/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PL  - England
TA  - J Anal Toxicol
JT  - Journal of analytical toxicology
JID - 7705085
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B)
RN  - 9EI49ZU76O (multidrug resistance protein 3)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B/genetics/*physiology
MH  - Animals
MH  - Biotransformation
MH  - Corpus Striatum/*metabolism
MH  - Data Interpretation, Statistical
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Molecular Structure
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*blood/chemistry/pharmacokinetics/toxicity
MH  - Neurotoxicity Syndromes/blood/etiology/genetics
MH  - Nonlinear Dynamics
MH  - Rats
MH  - Species Specificity
MH  - Stereoisomerism
MH  - Tissue Distribution
PMC - PMC6684102
MID - NIHMS1043926
EDAT- 2011/08/30 06:00
MHDA- 2012/01/13 06:00
PMCR- 2019/08/06
CRDT- 2011/08/30 06:00
PHST- 2011/08/30 06:00 [entrez]
PHST- 2011/08/30 06:00 [pubmed]
PHST- 2012/01/13 06:00 [medline]
PHST- 2019/08/06 00:00 [pmc-release]
AID - 10.1093/anatox/35.7.470 [doi]
PST - ppublish
SO  - J Anal Toxicol. 2011 Sep;35(7):470-80. doi: 10.1093/anatox/35.7.470.