PMID- 21295122
OWN - NLM
STAT- MEDLINE
DCOM- 20110603
LR  - 20131121
IS  - 1879-3169 (Electronic)
IS  - 0378-4274 (Linking)
VI  - 202
IP  - 2
DP  - 2011 Apr 25
TI  - Sulfation of the 3,4-methylenedioxymethamphetamine (MDMA) metabolites 
      3,4-dihydroxymethamphetamine (DHMA) and 4-hydroxy-3-methoxymethamphetamine (HMMA) 
      and their capability to inhibit human sulfotransferases.
PG  - 120-8
LID - 10.1016/j.toxlet.2011.01.026 [doi]
AB  - 3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy) is excreted in human urine 
      mainly as conjugates of its metabolites 3,4-dihydroxymethamphetamine (DHMA) and 
      4-hydroxy-3-methoxymethamphetamine (HMMA). The glucuronidation kinetics of HMMA 
      showed high capacities, but also high K(m) values, unlikely to be reached after 
      recreational user's doses. Therefore, the aim of the present work was to 
      investigate the sulfation of DHMA and HMMA by human sulfotransferases (SULTs) in 
      pooled human liver cytosol (pHLC). The kinetic data showed deviation from typical 
      Michaelis-Menten kinetics. The overall efficiency for HMMA sulfation was 
      calculated to be 2-10 times higher than for glucuronidation. As the sulfation of 
      both MDMA metabolites showed substrate inhibition effects, their inhibitory 
      potential towards typical sulfation reactions in pHLC was tested. The following 
      substrates for typical sulfation reactions were used: nitrophenol, dopamine, 
      estradiol, and dehydroepi androsten dione. Inhibition was observed towards 
      dopamine sulfation by DHMA and HMMA, but not by MDMA. The 1/V vs. 1/S plots 
      indicated a mixed-type or competitive inhibition model for DHMA and HMMA, 
      respectively. In conclusion, the presented data indicated that sulfation of HMMA 
      should be the major conjugation reaction observed in humans. Furthermore, both, 
      DHMA and HMMA, were identified as inhibitors of dopamine sulfation.
CI  - Copyright (c) 2011 Elsevier Ireland Ltd. All rights reserved.
FAU - Schwaninger, Andrea E
AU  - Schwaninger AE
AD  - Department of Experimental and Clinical Toxicology, Institute of Experimental and 
      Clinical Pharmacology and Toxicology, Saarland University, Kirrberger Strasse 1, 
      D-66421 Homburg (Saar), Germany.
FAU - Meyer, Markus R
AU  - Meyer MR
FAU - Zapp, Josef
AU  - Zapp J
FAU - Maurer, Hans H
AU  - Maurer HH
LA  - eng
PT  - Journal Article
DEP - 20110202
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Hallucinogens)
RN  - 0 (Mandelic Acids)
RN  - 117652-28-5 (4-hydroxy-3-methoxymethamphetamine)
RN  - 44RAL3456C (Methamphetamine)
RN  - 775-01-9 (3,4-dihydroxymandelic acid)
RN  - EC 2.8.2.- (Sulfotransferases)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Cytosol/drug effects/enzymology/metabolism
MH  - Dopamine/metabolism
MH  - Hallucinogens/*metabolism/toxicity
MH  - Humans
MH  - Kinetics
MH  - Mandelic Acids/*metabolism/toxicity
MH  - Methamphetamine/*analogs & derivatives/metabolism/toxicity
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*metabolism/toxicity
MH  - Sulfotransferases/*antagonists & inhibitors/metabolism
EDAT- 2011/02/08 06:00
MHDA- 2011/06/04 06:00
CRDT- 2011/02/08 06:00
PHST- 2010/12/16 00:00 [received]
PHST- 2011/01/25 00:00 [revised]
PHST- 2011/01/26 00:00 [accepted]
PHST- 2011/02/08 06:00 [entrez]
PHST- 2011/02/08 06:00 [pubmed]
PHST- 2011/06/04 06:00 [medline]
AID - S0378-4274(11)00044-0 [pii]
AID - 10.1016/j.toxlet.2011.01.026 [doi]
PST - ppublish
SO  - Toxicol Lett. 2011 Apr 25;202(2):120-8. doi: 10.1016/j.toxlet.2011.01.026. Epub 
      2011 Feb 2.