PMID- 1978728
OWN - NLM
STAT- MEDLINE
DCOM- 19901231
LR  - 20131121
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 255
IP  - 2
DP  - 1990 Nov
TI  - Selective 5-hydroxytryptamine2 receptor antagonists protect against the 
      neurotoxicity of methylenedioxymethamphetamine in rats.
PG  - 478-83
AB  - The serotonergic deficits resulting from methylenedioxymethamphetamine 
      (MDMA)-induced neurotoxicity were prevented by the simultaneous administration of 
      5-hydroxytryptamine2 (5-HT2) receptor antagonists such as MDL 11,939 or 
      ritanserin. This effect was not region specific as protection was observed in the 
      cortex, hippocampus and striatum 1 week after the administration of a single dose 
      of MDMA. MDL 11,939 also showed some efficacy at reducing the deficits in 5-HT 
      concentrations and tryptophan hydroxylase activity produced by multiple 
      administrations of MDMA. Protection against the neurotoxicity required the 
      administration of MDL 11,939 within 1 hr of MDMA indicating 5-HT2 receptor 
      activation was an early event in the process leading to terminal damage. 
      Examination of the effect of the 5-HT2 receptor blockade on the early 
      neurochemical alterations induced by MDMA revealed an inhibitory effect on 
      MDMA-stimulated dopamine synthesis. Analysis of these data and the associated 
      changes in dopamine metabolites indicates that 5-HT2 receptor antagonists block 
      MDMA-induced neurotoxicity by interfering with the ability of the dopamine neuron 
      to maintain its cytoplasmic pool of transmitter and thereby sustain 
      carrier-mediated dopamine release.
FAU - Schmidt, C J
AU  - Schmidt CJ
AD  - Merrell Dow Research Institute, Cincinnati, Ohio.
FAU - Abbate, G M
AU  - Abbate GM
FAU - Black, C K
AU  - Black CK
FAU - Taylor, V L
AU  - Taylor VL
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 (Receptors, Serotonin)
RN  - 0 (Serotonin Antagonists)
RN  - 333DO1RDJY (Serotonin)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
RN  - CK833KGX7E (Amphetamine)
RN  - EC 1.14.16.4 (Tryptophan Hydroxylase)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine/*analogs & derivatives/antagonists & 
      inhibitors/toxicity
MH  - Amphetamine/pharmacology
MH  - Animals
MH  - Brain/*drug effects
MH  - Cerebral Cortex/chemistry/drug effects
MH  - Dopamine/metabolism
MH  - Hippocampus/chemistry/drug effects
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Receptors, Serotonin/*drug effects
MH  - Serotonin/analysis
MH  - Serotonin Antagonists/*pharmacology
MH  - Tryptophan Hydroxylase/analysis
EDAT- 1990/11/01 00:00
MHDA- 1990/11/01 00:01
CRDT- 1990/11/01 00:00
PHST- 1990/11/01 00:00 [pubmed]
PHST- 1990/11/01 00:01 [medline]
PHST- 1990/11/01 00:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 1990 Nov;255(2):478-83.