PMID- 7903417
OWN - NLM
STAT- MEDLINE
DCOM- 19940126
LR  - 20141120
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 44
IP  - 6
DP  - 1993 Dec
TI  - Amphetamine derivatives interact with both plasma membrane and secretory vesicle 
      biogenic amine transporters.
PG  - 1227-31
AB  - The interaction of fenfluramine, 3,4-methylenedioxymethamphetamine (MDMA), and 
      p-chloroamphetamine (PCA) with the platelet plasma membrane serotonin transporter 
      and the vesicular amine transporter were studied using both transport and binding 
      measurements. Fenfluramine is apparently a substrate for the plasma membrane 
      transporter, and consequently inhibits both serotonin transport and imipramine 
      binding. Moreover, fenfluramine exchanges with internal [3H]serotonin in a plasma 
      membrane transporter-mediated reaction that requires NaCl and is blocked by 
      imipramine. These properties are similar to those of MDMA and PCA as previously 
      described. In adrenal chromaffin granule membrane vesicles containing the 
      vesicular amine transporter, fenfluramine inhibited serotonin transport and 
      dissipated the transmembrane pH difference (delta pH) that drives amine uptake. 
      The use of [3H]reserpine-binding measurements to determine drug interaction with 
      the vesicular amine transporter allowed assessment of the relative ability of 
      MDMA, PCA, and fenfluramine to bind to the substrate site of the vesicular 
      transporter. These measurements permit a distinction between inhibition of 
      vesicular serotonin transport by directly blocking vesicular amine transport and 
      by dissipating delta pH. The results indicate that MDMA and fenfluramine inhibit 
      by both mechanisms but PCA dissipates delta pH without blocking vesicular amine 
      transport directly.
FAU - Schuldiner, S
AU  - Schuldiner S
AD  - Department of Pharmacology, Yale University School of Medicine, New Haven, CT 
      06510.
FAU - Steiner-Mordoch, S
AU  - Steiner-Mordoch S
FAU - Yelin, R
AU  - Yelin R
FAU - Wall, S C
AU  - Wall SC
FAU - Rudnick, G
AU  - Rudnick G
LA  - eng
GR  - DA 07295/DA/NIDA NIH HHS/United States
GR  - NS 16708/NS/NINDS 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 (Carrier Proteins)
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  - 2DS058H2CF (Fenfluramine)
RN  - 333DO1RDJY (Serotonin)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
RN  - 64-12-0 (p-Chloroamphetamine)
RN  - 8B1QWR724A (Reserpine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine/*analogs & derivatives/pharmacology
MH  - Animals
MH  - Blood Platelets/drug effects/metabolism
MH  - Carrier Proteins/*drug effects
MH  - Cattle
MH  - Cell Membrane/drug effects/metabolism
MH  - Chromaffin Granules/drug effects/metabolism
MH  - Fenfluramine/*pharmacology
MH  - Humans
MH  - In Vitro Techniques
MH  - Membrane Glycoproteins/*drug effects
MH  - *Membrane Transport Proteins
MH  - N-Methyl-3,4-methylenedioxyamphetamine
MH  - *Nerve Tissue Proteins
MH  - Reserpine/metabolism
MH  - Serotonin/*metabolism
MH  - Serotonin Plasma Membrane Transport Proteins
MH  - p-Chloroamphetamine/*pharmacology
EDAT- 1993/12/01 00:00
MHDA- 1993/12/01 00:01
CRDT- 1993/12/01 00:00
PHST- 1993/12/01 00:00 [pubmed]
PHST- 1993/12/01 00:01 [medline]
PHST- 1993/12/01 00:00 [entrez]
PST - ppublish
SO  - Mol Pharmacol. 1993 Dec;44(6):1227-31.