recovery time for ecstacy induced serotonin recepter damage???

Liar42 liar42 at aol.com
Sat Nov 3 16:08:59 EST 2001


And maybe the dependency comes also from you, because you took E often enough
to mess up enough in the first place, and not just not at all or so rarely,
that it did not mess up much, and next you go and stuff some other drug in
after you got some problems of the first, and call drug stuff to feel normal.

And with anxieties you do not look at what these are naturally regarded and
your attitudes there.

In other words you do ot just let withdrawal effects wash past 
and with anxieties work on your attitudes,
but instead complain about effects from one drug and then go and stuff in the
next, and then you find yourself to "feel perfectly normal".

As an old acidhead I save me a longer comment on that.

%%%%%%%%%%


However you can have texts someone else here in this room posted about the
topic ecstasy:

The new class of drugs like GBH, which are very potent and potentially very
destructive, should be a major public health concern.

&&&&&&&&&


Extract from below article notes, Molecular Mechanism of the Inactivation of
Tryptophan Hydroxylase by Nitric Oxide: Attack on Critical Sulfhydryls that
Spare the Enzyme Iron Center
:

Selected amphetamines have profound effects on the 5-HT neuronal system.
Methylenedioxymethamphetamine (ecstasy) (MDMA) and p-chloroamphetamine cause
extensive destruction of 5-HT neurons
...
The recent demonstration that TPH is inactivated by NO in vitro (Kuhn and
Arthur, 1996, 1997) establishes the possibility that this important brain
enzyme is susceptible to inactivation by NO in vivo and could form the basis
for loss of TPH activity when NO levels are elevated in brain (e.g.,
amphetamine-induced).

&&&&&&&&&


Article: Molecular Mechanism of the Inactivation of Tryptophan Hydroxylase
by Nitric Oxide: Attack on Critical Sulfhydryls that Spare the Enzyme Iron
Center
Authors: Donald M. Kuhn 1,2 and Robert Arthur Jr 1
Journal: The Journal of Neuroscience, October 1, 1997, 17(19):7245-7251
Location:
N\Ni
NOS inhibits serotonin via tryto hyrodrox
Date obtained: 31/01/00
Web Page:
Date Read: 27/02/00
Date to Review: 15/10/00
Keywords:
Key words: tryptophan hydroxylase; nitric oxide; sulfhydryls;
catalytic iron site; serotonin; neurotoxic amphetamines, nos, flf, ros,
aspartmane,
ecstasy, mdma, 5ht neurons, depression,
Printed:
No = subject: 1
Notes:
Tryptophan hydroxylase (TPH), the initial and rate-limiting en-zyme in the
biosynthesis of the neurotransmitter serotonin (5- HT), is irreversibly
inactivated by nitric oxide (NO). We have expressed brain TPH as a
recombinant glutathione-S-transferase fusion protein and delineated the
catalytic domain of the enzyme as the region spanning amino acids 99-444.
Highly purified TPH catalytic core, like the native enzyme from brain, is
inactivated by NO in a concentration-dependent man-ner. Removal of iron from
TPH produces an apoenzyme with low activity that can be reconverted to its
highly active holo-form by the addition of ferrous iron. Apo-TPH exposed to
NO cannot be reactivated by iron. Treatment of holo-TPH (iron-loaded) with
the disulfide 5,59-dithio-bis (2-nitrobenzoic acid) (DTNB) causes an
inactivation of TPH that is readily reversed by dithiothreitol (DTT).
DTNB-treated TPH [sulfhydryl (SH)-protected] exposed to NO is returned to
full activity by thiol reduction with DTT. The inactivation of native TPH by
NO cannot be reversed by either iron or DTT. These data indicate that NO
inactivates TPH by selective action on critical SH groups (i.e., cysteine
residues) while sparing catalytic iron sites within the enzyme. The results
are interpreted with reference to the substituted amphetamines, which are
neurotoxic to 5-HT neurons, that inactivate TPH in vivo and are now known to
produce NO and other reactive oxygen species in vivo.
--
Selected amphetamines have profound effects on the 5-HT neuronal system.
Methylenedioxymethamphetamine (ecstasy) (MDMA) and p-chloroamphetamine cause
extensive destruction of 5-HT neurons. An early manifestation of their
effects is a significant inactivation of TPH (for reviews, see Gibb et al.,
1993; Steele et al., 1994; Seiden and Sabol, 1996). The mechanisms
underlying these effects on TPH are not known, but emerging data implicate
drug-induced production of reactive oxygen species (ROS) and nitric oxide
(NO). The cellular effects of ROS or NO cannot be predicted a priori: NO can
be toxic to some cells (Lipton et al., 1993; Dawson et al., 1994), it is a
neurotransmitter- neuromodulator in other cells (Jaffrey and Snyder, 1996),
and it can protect still other cells from known toxins (Wink et al., 1995,
1996). The recent demonstration that TPH is inactivated by NO in vitro (Kuhn
and Arthur, 1996, 1997) establishes the possibility that this important
brain enzyme is susceptible to inactivation by NO in vivo and could form the
basis for loss of TPH activity when NO levels are elevated in brain (e.g.,
amphetamine-induced).
--
 By altering independently the iron or SH status of TPH, we demon-strate
that NO inactivates TPH by selective attack on critical SH groups, sparing
catalytic iron sites altogether.
--
These experiments establish the importance of iron in TPH f unc-tion and
demonstrate that TPH can be reversibly converted be-tween the apo- and
holo-forms.
--
The present results lead to several interesting conclusions about TPH.
First, they reaffirm the importance of iron and SH groups (free cysteines)
in TPH catalytic f unction. Second, they establish the feasibility and value
of using highly purified, recom-binant TPH to probe the molecular mechanisms
regulating this enzyme. Finally, they point to SH groups as targets for
NO-induced inactivation of the enzyme.
-------------

16/12/98 22:04

Adverse neuropsychiatric events associated with dexfenfluramine and
fenfluramine.

McCann UD, Eligulashvili V, Ricaurte GA
Biological Psychiatry Branch, National Institute of Mental Health, Bethesda,
MD, USA.

[Medline record in process]

Positron emission tomographic evidence of toxic effect of MDMA ("Ecstasy")
on brain serotonin neurons in human beings.

McCann UD, Szabo Z, Scheffel U, Dannals RF, Ricaurte GA
Biological Psychiatry Branch, National Institute of Mental Health, Bethesda,
Maryland, USA.

BACKGROUND: (+/-)3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") is a
popular recreational drug that selectively damages brain serotonin (5-HT)
neurons in animals at doses that closely approach those used by humans. We
investigated the status of brain 5-HT neurons in MDMA users. METHODS: We
enrolled 14 previous users of MDMA who were currently abstaining from use
and 15 controls who had never used MDMA. We used positron emission
tomography (PET) with the radioligand carbon-11-labelled McN-5652, which
selectively labels the 5-HT transporter. We analysed whether there were
differences in 5-HT transporter binding between abstinent MDMA users and
participants in the control group. Blood and urine samples were taken and
tested to check for abstinence. FINDINGS: MDMA users showed decreased global
and regional brain 5-HT transporter binding compared with controls.
Decreases in 5-HT transporter binding positively correlated with the extent
of previous MDMA use. INTERPRETATION: Quantitative PET studies with a ligand
selective for 5-HT transporters can be used to assess the status of 5-HT
neurons in the living human brain. We show direct evidence of a decrease in
a structural component of brain 5-HT neurons in human MDMA user

MDMA-induced neurotoxicity: parameters of degeneration and recovery of brain
serotonin neurons.

Battaglia G, Yeh SY, De Souza EB
Neuroscience Branch, National Institute on Drug Abuse, Baltimore, MD 21224.

This study investigates a number of parameters that influence the neurotoxic
effects of 3,4-methylenedioxymethamphetamine (MDMA) on serotonin (5-HT)
neurons in brain. Both the dose and number of injections of MDMA affect the
degree of neurotoxicity on 5-HT axons and terminals as assessed by decreases
in the content of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) and the
density of 5-HT uptake sites. Repeated systemic administration of various
doses of MDMA (5-20 mg/kg twice daily for 4 consecutive days) results in
dose-dependent decreases in 5-HT, 5-HIAA and 5-HT uptake sites. Increasing
the number of injections of MDMA resulted in progressively greater
reductions in 5-HT and 5-HIAA which occurred prior to decreases in 5-HT
uptake sites. In contrast, no significant changes were observed in the
density of norepinephrine uptake sites following single or repeated
injections of 20 mg/kg MDMA. With respect to neuronal regeneration,
following an initial 90% loss of 5-HT uptake sites after treatment with
MDMA, the recovery of these sites occurred over a protracted period of time;
a marked 25% reduction was seen at 6 months and the concentration of 5-HT
uptake sites returned to control levels at 12 months following treatment
with MDMA. Pretreatment with the selective 5-HT uptake blocker, citalopram,
prior to each injection of MDMA prevented the neurotoxic effects of MDMA on
the 5-HT parameters described above suggesting that active uptake of MDMA or
a MDMA-related substance into brain 5-HT neurons was involved in the
neurotoxic actions of the drug. In addition, the neurodegenerative effects
of MDMA on 5-HT neurons exhibited some species specificity as comparable
decreases in cerebral cortical 5-HT, 5-HIAA and 5-HT uptake sites were
observed in rat and guinea pig while no significant changes in any of these
serotonergic parameters were seen in mouse brain.

PMID: 2452449, UI: 88203802

%%%%%%%%%%%%%%%%

So maybe with the: >I just need to know if any body knows how long this would
last for<
goggle longer at the:
"25% reduction was seen at 6 months and the concentration of 5-HT
uptake sites returned to control levels at 12 months"

However I criticized your attitudes further up;
they might lead you into troubles again in the future
and are not good for internal balances of other systems in your head&body.

(But with my unhealthy life style I am of course just the perfect one as an
example for good health, hehe ... ;-)

Ci.




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