PMID- 10580546
OWN - NLM
STAT- MEDLINE
DCOM- 19991229
LR  - 20191103
IS  - 0742-2091 (Print)
IS  - 0742-2091 (Linking)
VI  - 15
IP  - 3
DP  - 1999 Jun
TI  - The neurotoxic effects of methylenedioxymethamphetamine (MDMA) and its 
      metabolites on rat brain spheroids in culture.
PG  - 137-42
AB  - Rat whole-brain spheroids were used to assess the intrinsic neurotoxicity of 
      methylenedioxy-methamphetamine (MDMA, Ecstasy) and two of its metabolites, 
      dihydroxymethamphetamine (DHMA) and 6-hydroxy-MDMA (6-OH MDMA). Exposure of brain 
      spheroids to MDMA or the metabolite 6-OH MDMA (up to 500 micromol/L) for 5 days 
      in culture did not alter intracellular levels of glutathione (GSH), glial 
      fibrillary acidic protein (GFAP) or serotonin (5-HT). In contrast, exposure to 
      the metabolite DHMA, which can deplete intracellular thiols, significantly 
      increased GSH levels (up to 170% of control) following exposure to 50 and 100 
      micromol/L DHMA. There was also a significant reduction in the levels of glial 
      fibrillary acidic protein (GFAP) and GSH by DHMA at the highest concentration 
      tested (500 micromol/L) but there was no effect on 5HT. This may constitute a 
      sublethal neurotoxic compensatory response to DHMA in an attempt to replenish 
      depleted intraneural GSH levels following metabolite exposure. Rat whole-brain 
      spheroids may thus be a useful in vitro model to delineate mechanisms and effects 
      of this class of neurotoxin.
FAU - Walker, T M
AU  - Walker TM
AD  - Department of Strategic Toxicological Sciences, GlaxoWellcome, Ware, Herts, UK.
FAU - Davenport-Jones, J E
AU  - Davenport-Jones JE
FAU - Fox, R M
AU  - Fox RM
FAU - Atterwill, C K
AU  - Atterwill CK
LA  - eng
PT  - Journal Article
PL  - Switzerland
TA  - Cell Biol Toxicol
JT  - Cell biology and toxicology
JID - 8506639
RN  - 0 (Biomarkers)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Serotonin Agents)
RN  - 136706-34-8 (6-hydroxy-N-methyl-3,4-methylenedioxyamphetamine)
RN  - 15398-87-5 (alpha-methylepinine)
RN  - 333DO1RDJY (Serotonin)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - GAN16C9B8O (Glutathione)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - R7339QLN1C (Deoxyepinephrine)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine/*analogs & derivatives/metabolism/toxicity
MH  - Animals
MH  - Biomarkers
MH  - Brain/cytology/*drug effects/enzymology/metabolism
MH  - Brain Diseases/*chemically induced/enzymology/metabolism
MH  - Cytosol/enzymology
MH  - Deoxyepinephrine/*analogs & derivatives/metabolism/toxicity
MH  - Dose-Response Relationship, Drug
MH  - Fetus
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Glutathione/metabolism
MH  - L-Lactate Dehydrogenase/metabolism
MH  - N-Methyl-3,4-methylenedioxyamphetamine/metabolism/*toxicity
MH  - Rats
MH  - Serotonin/metabolism
MH  - Serotonin Agents/metabolism/*toxicity
MH  - Spheroids, Cellular/*drug effects
EDAT- 1999/12/02 00:00
MHDA- 1999/12/02 00:01
CRDT- 1999/12/02 00:00
PHST- 1999/12/02 00:00 [pubmed]
PHST- 1999/12/02 00:01 [medline]
PHST- 1999/12/02 00:00 [entrez]
AID - 10.1023/a:1007658501306 [doi]
PST - ppublish
SO  - Cell Biol Toxicol. 1999 Jun;15(3):137-42. doi: 10.1023/a:1007658501306.