PMID- 8429828
OWN - NLM
STAT- MEDLINE
DCOM- 19930309
LR  - 20141120
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 43
IP  - 2
DP  - 1993 Feb
TI  - Non-neurotoxic amphetamine derivatives release serotonin through serotonin 
      transporters.
PG  - 271-6
AB  - 3,4-Methylenedioxymethamphetamine (MDMA) and several other amphetamine 
      derivatives cause degeneration of serotonergic nerve terminals. These drugs also 
      release serotonin from nerve terminals both in vivo and in vitro. Two 
      non-neurotoxic derivatives of MDMA were tested in membrane vesicle model systems 
      to determine whether they also lacked the ability to release serotonin. 
      3-Methoxy-4-methylamphetamine (MMA) and 5-methoxy-6-methyl-2-aminoindan (MMAI) 
      both inhibited imipramine binding to serotonin transporters in platelet plasma 
      membrane vesicles and both inhibited Na+ gradient-driven serotonin transport into 
      those vesicles. Significantly, both MMA and MMAI released [3H]serotonin from 
      plasma membrane vesicles, apparently by a process of exchange. The half-maximal 
      concentrations for this effect were comparable to that reported for MDMA. In 
      addition to their effects on plasma membrane transporters, MMA and MMAI both 
      inhibited serotonin transport into chromaffin granule membrane vesicles catalyzed 
      by the vesicular biogenic amine transporter. At higher concentrations, these 
      compounds also caused release of [3H]serotonin from chromaffin granule membrane 
      vesicles and dissipated the transmembrane pH difference (delta pH). Although MMAI 
      effects on the serotonin transporter were similar to those of MDMA, the two 
      compounds had different effects on dopamine transporters. MDMA and 
      methamphetamine inhibited binding of a cocaine analog to the dopamine transporter 
      and released dopamine accumulated by cells expressing dopamine transporters, but 
      similar concentrations of MMAI were inactive.
FAU - Rudnick, G
AU  - Rudnick G
AD  - Department of Pharmacology, Yale University School of Medicine, New Haven, 
      Connecticut 06510.
FAU - Wall, S C
AU  - Wall SC
LA  - eng
GR  - DA07259/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Amphetamines)
RN  - 0 (Carrier Proteins)
RN  - 0 (Indans)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (SLC6A4 protein, human)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 124206-66-2 (3-methoxy-4-methylamphetamine)
RN  - 132980-16-6 (5-methoxy-6-methyl-2-aminoindan)
RN  - 333DO1RDJY (Serotonin)
RN  - 44RAL3456C (Methamphetamine)
RN  - OGG85SX4E4 (Imipramine)
SB  - IM
MH  - Amphetamines/*pharmacology
MH  - Blood Platelets/drug effects
MH  - Carrier Proteins/*drug effects/metabolism
MH  - Cell Membrane/drug effects
MH  - Chromaffin Granules/drug effects
MH  - Humans
MH  - Imipramine/metabolism
MH  - In Vitro Techniques
MH  - Indans/pharmacology
MH  - Membrane Glycoproteins/*drug effects/metabolism
MH  - *Membrane Transport Proteins
MH  - Methamphetamine/analogs & derivatives/pharmacology
MH  - Models, Biological
MH  - Nerve Endings/*drug effects/metabolism
MH  - *Nerve Tissue Proteins
MH  - Radioligand Assay
MH  - Serotonin/*metabolism
MH  - Serotonin Plasma Membrane Transport Proteins
EDAT- 1993/02/01 00:00
MHDA- 1993/02/01 00:01
CRDT- 1993/02/01 00:00
PHST- 1993/02/01 00:00 [pubmed]
PHST- 1993/02/01 00:01 [medline]
PHST- 1993/02/01 00:00 [entrez]
PST - ppublish
SO  - Mol Pharmacol. 1993 Feb;43(2):271-6.