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Some amphetamine affinities

John H. johnhas at tpg.com.au
Sun Feb 15 10:40:57 EST 2004

Ah well bout time I tried the old Pubmed. PS people: Scirus.com is a
good search engine with some good advanced search features and
incorporates Pub med into its searches:


Anyway, BilZor, hope this helps, found on pub med. I suspect these
won't directly address your question but the contained refs in the
articles just might ... . It's like that with search engines but Me &
Co are hoping to change all that in about 5 years ...

J Biol Chem. 1994 Mar 11;269(10):7231-7.  Related Articles, Links  


Furthermore, methamphetamine preferentially inhibits transport by SVAT
relative to CGAT, apparently by competing at the site of amine
recognition rather than by disrupting the vesicular pH gradient.

The chromaffin granule and synaptic vesicle amine transporters differ
in substrate recognition and sensitivity to inhibitors.

Peter D, Jimenez J, Liu Y, Kim J, Edwards RH.

Department of Microbiology and Immunology, UCLA School of Medicine

Classical studies using bovine chromaffin granules have defined the
physiologic and pharmacologic properties of the vesicular amine
transporter that packages monoamine transmitters into intracellular
vesicles for subsequent regulated release. The recent isolation of two
distinct but closely related cDNA clones encoding vesicular amine
transport suggests that the activity expressed in the brain (synaptic
vesicle amine transporter or SVAT) may differ significantly from the
previously described adrenal gland activity (chromaffin granule amine
transporter or CGAT). A direct comparison of the two transporters now
shows that SVAT has a higher affinity than CGAT for monoamine
substrates, in particular for histamine. In addition, SVAT shows
approximately 10-fold greater sensitivity to tetrabenazine than CGAT.
[3H]Dihydrotetrabenazine shows no detectable binding to CGAT but does
bind to SVAT, accounting for the differential sensitivity.
Furthermore, methamphetamine preferentially inhibits transport by SVAT
relative to CGAT, apparently by competing at the site of amine
recognition rather than by disrupting the vesicular pH gradient. These
previously unsuspected differences in the storage of monoamine
transmitter in the central nervous system and the adrenal gland may
help to account for several classic pharmacological observations.

PMID: 8125935 [PubMed - indexed for MEDLINE] 

 Brain Res. 1998 Jan 26;782(1-2):219-27.  Related Articles, Links  

Methamphetamine-induced alterations in dopamine transporter function.

Bennett BA, Hollingsworth CK, Martin RS, Harp JJ.

Department of Physiology and Pharmacology, Bowman Gray School of
Medicine, Winston-Salem, NC 27157, USA.
bbennett at medcenter.wpmail.wfu.edu

Repeated methamphetamine (METH) administration has been shown to
produce differing neurochemical as well as behavioral effects in rats.
This study was designed to examine the effects of acute and chronic
METH exposure on uptake and release of [3H]dopamine (DA) in cultured
midbrain dopamine neurons to determine if persistent neuronal
adaptations ensue. In addition, we have assessed DA D2 receptor
function to determine if chronic METH alters this receptor. Fetal
midbrain cultures were exposed to METH (1, 10 microM) for 5 days and
dopaminergic function examined 1 or 7 days after drug removal. The
ability of METH to release [3H]DA was compared to other releasing
agents as well as several potent uptake inhibitors. Chronic exposure
to a release-promoting concentration of METH resulted in either no
change or a reduction in [3H]DA release upon subsequent METH
challenge. Pretreatment with METH was also found to cause a decrease
in the Bmax for [3H]raclopride binding, suggesting that persistently
elevated DA levels cause a downregulation of DA D2 receptors.
Examination of transporter kinetics utilizing initial velocity of
uptake revealed that METH treatment caused a significant decrease in
affinity (K(m)) for the substrate (DA), while not altering the maximal
velocity of uptake (Vmax). Binding studies with [125I]RTI-55 revealed
that there was no alteration in either the Bmax or Kd for this ligand,
suggesting that the changes induced by METH treatment are due to
alterations in K(m) and not in the number of DA transport sites. The
results from these studies indicate that METH treatment produces a
modification in transporter function which may be associated with both
the altered uptake and release of [3H]DA. These changes have broad
implications for the regulation of transporter activity not only
because of the relevance to pre-synaptic mechanisms controlling
neurotransmission, but also to the importance of the neuronal
adaptation that occurs in response to chronic METH exposure.

PMID: 9519266 [PubMed - indexed for MEDLINE] 

Synapse. 2000 Mar 1;35(3):222-7.  Related Articles, Links  

Neurochemical neutralization of methamphetamine with high-affinity
nonselective inhibitors of biogenic amine transporters: a
pharmacological strategy for treating stimulant abuse.

Rothman RB, Partilla JS, Baumann MH, Dersch CM, Carroll FI, Rice KC.

Clinical Psychopharmacology Section, Intramural Research Program,

The abuse of methamphetamine (METH) and other amphetamine-like
stimulants is a growing problem in the United States. METH is a
substrate for the 12-transmembrane proteins which function as
transporters for the biogenic amines dopamine (DA), serotonin (5-HT),
and norepinephrine (NE). Increased release of CNS DA is thought to
mediate the addictive effects of METH, whereas increased release of NE
in both the peripheral and CNS is thought to mediate its
cardiovascular effects. The neurotoxic effects of METH on both
dopaminergic and serotonergic nerves requires the transport of METH
into the nerve terminals. Thus, transport of METH into nerve terminals
is the crucial first step in the production of METH-associated
pharmacological and toxicological effects. A single molecular entity
which would block the transport of METH at all three biogenic amine
transporters might function to neurochemically neutralize METH. This
agent would ideally be a high-affinity slowly dissociating agent at
all three transporters, and also be amenable to formulation as a
long-acting depot medication, such as has been accomplished with an
analog of GBR12909. As a first step towards developing such an agent,
we established an in vitro assay which selectively detects transporter
substrates and used this assay to profile the ability of a lead
compound, indatraline, to block the releasing effects of METH and MDMA
at the DA, 5-HT, and NE transporters. The major finding reported here
is that indatraline blocks the ability of METH and MDMA to release
these neurotransmitters. Synapse 35:222-227, 2000. Published 2000
Wiley-Liss, Inc.

PMID: 10657029 [PubMed - indexed for MEDLINE] 

BilZ0r <BilZ0r at TAKETHISOUThotmail.com> wrote in message news:<Xns948FB68E74FD3BilZ0rhotmailcom at>...
> Not that I'm really asking anyone here to do research for me, but no one 
> here would happen to be close to some information which says what affinity,  
> methamphetamine, mdma and mda have for the serotonin and dopamine reuptake 
> carrier, would they?

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