PMID- 2433425
OWN - NLM
STAT- MEDLINE
DCOM- 19870227
LR  - 20131121
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 240
IP  - 1
DP  - 1987 Jan
TI  - Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine.
PG  - 1-7
AB  - The neurochemical effects of the unique psychedelic agent, 
      methylenedioxymethamphetamine (MDMA), indicate it may be a serotonergic 
      neurotoxin related to agents such as p-chloroamphetamine. MDMA had a biphasic 
      effect on cortical serotonin concentrations beginning with an acute depletion of 
      the transmitter which reached a maximum between 3 and 6 hr after drug 
      administration. This early phase of depletion was reversible because cortical 
      serotonin concentrations had recovered to control levels by 24 hr. However, 
      transmitter concentrations were reduced significantly 1 week later, indicating a 
      second phase of depletion. The latter phase of depletion was associated with a 
      decrease in synaptosomal [3H]serotonin uptake due to a loss in the number of 
      uptake sites with no change in the affinity of the carrier for serotonin. This 
      neurotoxic effect of MDMA was found to be a property of the (+)-stereoisomer of 
      the drug as only this enantiomer produced the depletion of cortical serotonin and 
      the decrease in synaptosomal serotonin uptake at 1 week. In contrast to this, 
      both stereoisomers of the drug could produce the acute depletion of cortical 
      serotonin measured 3 hr after drug administration. Coadministration of the 
      selective serotonin uptake inhibitor, fluoxetine, completely blocked the 
      reduction in cortical serotonin concentrations 1 week after MDMA. Administration 
      of fluoxetine at various times after MDMA revealed that the long-term effects of 
      the drug developed independently of the acute depletion of serotonin and could be 
      partially blocked by the uptake inhibitor as long as 6 hr after drug 
      administration.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Schmidt, C J
AU  - Schmidt CJ
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Amphetamines)
RN  - 01K63SUP8D (Fluoxetine)
RN  - 333DO1RDJY (Serotonin)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
RN  - 54-16-0 (Hydroxyindoleacetic Acid)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine/analogs & derivatives/*toxicity
MH  - Amphetamines/*toxicity
MH  - Animals
MH  - Brain/*drug effects/metabolism
MH  - Cerebral Cortex/metabolism
MH  - Fluoxetine/pharmacology
MH  - Hydroxyindoleacetic Acid/metabolism
MH  - Kinetics
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Serotonin/metabolism
MH  - Stereoisomerism
MH  - Time Factors
EDAT- 1987/01/01 00:00
MHDA- 1987/01/01 00:01
CRDT- 1987/01/01 00:00
PHST- 1987/01/01 00:00 [pubmed]
PHST- 1987/01/01 00:01 [medline]
PHST- 1987/01/01 00:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 1987 Jan;240(1):1-7.