PMID- 12354291
OWN - NLM
STAT- MEDLINE
DCOM- 20021022
LR  - 20190630
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 82
IP  - 6
DP  - 2002 Sep
TI  - p-Methylthioamphetamine and 1-(m-chlorophenyl)piperazine, two non-neurotoxic 5-HT 
      releasers in vivo, differ from neurotoxic amphetamine derivatives in their mode 
      of action at 5-HT nerve endings in vitro.
PG  - 1435-43
AB  - The mechanism underlying the serotoninergic neurotoxicity of some amphetamine 
      derivatives, such as p-chloroamphetamine (pCA) and 
      3,4-methylenedioxymethamphetamine (MDMA), is still debated. Their main acute 
      effect, serotonin (5-HT) release from nerve endings, involves their interaction 
      with 5-HT transporters (SERTs), as substrates. Although this interaction is 
      required for the neurotoxic effects, 5-HT release alone may not be sufficient to 
      induce long-term 5-HT deficits. Some non-neurotoxic compounds, including 
      p-methylthioamphetamine (MTA) and 1-(m-chlorophenyl)piperazine (mCPP), have 5-HT 
      releasing properties in vivo and in brain slices comparable to that of neurotoxic 
      amphetamine derivatives. We measured 5-HT release in superfused rat brain 
      synaptosomes preloaded with [3H]5-HT, a model that distinguishes a releasing 
      effect from reuptake inhibition. MTA and mCPP induced much lower release than pCA 
      and MDMA. The striking difference between our findings in synaptosomes and those 
      obtained in vivo or in brain slices is probably related to a different 
      compartmentalisation of 5-HT in the different experimental models. Studies in 
      synaptosomes, where the vesicular storage of 5-HT is predominant, could therefore 
      bring to light differences between neurotoxic and non-neurotoxic 5-HT releasing 
      agents which cannot be appreciated in other experimental models and might be 
      useful to identify the mechanisms responsible for the neurotoxicity induced by 
      amphetamine derivatives.
FAU - Gobbi, M
AU  - Gobbi M
AD  - Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche 
      Farmacologiche Mario Negri, Italy. Gobbi@marionegri.it
FAU - Moia, M
AU  - Moia M
FAU - Pirona, L
AU  - Pirona L
FAU - Ceglia, I
AU  - Ceglia I
FAU - Reyes-Parada, M
AU  - Reyes-Parada M
FAU - Scorza, C
AU  - Scorza C
FAU - Mennini, T
AU  - Mennini T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Amphetamines)
RN  - 0 (Carrier Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Piperazines)
RN  - 0 (Serotonin Agents)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Slc6a4 protein, rat)
RN  - 0DHU5B8D6V (Citalopram)
RN  - 10028-17-8 (Tritium)
RN  - 333DO1RDJY (Serotonin)
RN  - 64-12-0 (p-Chloroamphetamine)
RN  - 6JP2T8KXTR (4-methylthioamphetamine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - REY0CNO998 (1-(3-chlorophenyl)piperazine)
SB  - IM
MH  - Amphetamines/*pharmacology
MH  - Animals
MH  - Binding, Competitive/drug effects
MH  - Brain Chemistry
MH  - Carrier Proteins/metabolism
MH  - Citalopram/pharmacokinetics
MH  - Dose-Response Relationship, Drug
MH  - Hippocampus/drug effects/metabolism
MH  - Membrane Glycoproteins/metabolism
MH  - *Membrane Transport Proteins
MH  - Microdialysis
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Nerve Endings/chemistry/*drug effects/metabolism
MH  - *Nerve Tissue Proteins
MH  - Piperazines/*pharmacology
MH  - Rats
MH  - Serotonin/*metabolism/pharmacokinetics
MH  - Serotonin Agents/pharmacology/toxicity
MH  - Serotonin Plasma Membrane Transport Proteins
MH  - Synaptosomes/chemistry/drug effects/metabolism
MH  - Tritium
MH  - p-Chloroamphetamine/*toxicity
EDAT- 2002/10/02 04:00
MHDA- 2002/10/31 04:00
CRDT- 2002/10/02 04:00
PHST- 2002/10/02 04:00 [pubmed]
PHST- 2002/10/31 04:00 [medline]
PHST- 2002/10/02 04:00 [entrez]
AID - 1073 [pii]
AID - 10.1046/j.1471-4159.2002.01073.x [doi]
PST - ppublish
SO  - J Neurochem. 2002 Sep;82(6):1435-43. doi: 10.1046/j.1471-4159.2002.01073.x.