PMID- 1899117
OWN - NLM
STAT- MEDLINE
DCOM- 19910222
LR  - 20131121
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 256
IP  - 1
DP  - 1991 Jan
TI  - 5-HT2 antagonists stereoselectively prevent the neurotoxicity of 
      3,4-methylenedioxymethamphetamine by blocking the acute stimulation of dopamine 
      synthesis: reversal by L-dopa.
PG  - 230-5
AB  - The active and inactive stereoisomers of the serotonin (5-HT2) antagonist, MDL 
      11,939, were used to examine the relationship between the acute effects of 
      3,4-methylenedioxymethamphetamine (MDMA) on the dopaminergic system and its 
      long-term effects on the serotonergic system. Only the R-(+) stereoisomer of MDL 
      11,939 both reversed the acute stimulation of striatal dopamine synthesis by MDMA 
      and prevented the deficit in forebrain 5-HT concentrations measured one week 
      later. This acute activation of striatal dopamine synthesis by MDMA is a 
      compensatory response to the carrier-mediated efflux of transmitter as shown by 
      its sensitivity to the dopamine uptake inhibitor, nomifensine. It is suggested 
      that in the absence of this enhanced synthesis, the dopaminergic neuron cannot 
      sustain the carrier-mediated dopamine release which is a prerequisite for the 
      development of MDMA-induced neurotoxicity. This hypothesis is supported by the 
      observation that the administration of the dopamine precursor, L-dopa, with MDMA 
      reverses the protective effects of 5-HT2 receptor antagonists.
FAU - Schmidt, C J
AU  - Schmidt CJ
AD  - Merrell Dow Research Institute, Cincinnati, Ohio.
FAU - Taylor, V L
AU  - Taylor VL
FAU - Abbate, G M
AU  - Abbate GM
FAU - Nieduzak, T R
AU  - Nieduzak TR
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Anti-Arrhythmia Agents)
RN  - 0 (Piperidines)
RN  - 0 (Serotonin Antagonists)
RN  - 102-32-9 (3,4-Dihydroxyphenylacetic Acid)
RN  - 107703-78-6 (alpha-phenyl-1-(2-phenylethyl)-4-piperidinemethanol)
RN  - 145TFV465S (Ritanserin)
RN  - 1LGS5JRP31 (Nomifensine)
RN  - 46627O600J (Levodopa)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
RN  - J6292F8L3D (Haloperidol)
RN  - VTD58H1Z2X (Dopamine)
RN  - X77S6GMS36 (Homovanillic Acid)
SB  - IM
MH  - 3,4-Dihydroxyphenylacetic Acid/metabolism
MH  - 3,4-Methylenedioxyamphetamine/administration & dosage/*toxicity
MH  - Animals
MH  - Anti-Arrhythmia Agents/pharmacology
MH  - Brain/*drug effects/metabolism
MH  - Corpus Striatum/drug effects/metabolism
MH  - Dopamine/*biosynthesis/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Drug Synergism
MH  - Haloperidol/pharmacology
MH  - Homovanillic Acid/metabolism
MH  - Levodopa/metabolism/pharmacology
MH  - Male
MH  - Nomifensine/pharmacology
MH  - Piperidines/pharmacology
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Ritanserin
MH  - Serotonin Antagonists/*pharmacology/therapeutic use
MH  - Stereoisomerism
MH  - Time Factors
EDAT- 1991/01/01 00:00
MHDA- 1991/01/01 00:01
CRDT- 1991/01/01 00:00
PHST- 1991/01/01 00:00 [pubmed]
PHST- 1991/01/01 00:01 [medline]
PHST- 1991/01/01 00:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 1991 Jan;256(1):230-5.