Pondimin (fenfluramine) 
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 Pondimin (fenfluramine)

i'm passing the following information along from an authoritiative
friend who prefers to remain anonymous:

Date: Tue, 24 May 94 16:07:14 -0500
From: [a well-known medicinal chemist]

Interneuron is awaiting FDA approval to market Dexfenfluramine through
Lederle Laboratories in the U.S.  It is big in Europe, but the expertes seem
to think it doesn't work that well.  Studies showing it caused very modest
weight loss (6-8 lbs?) were coupled with a stringent dietary regimen.  There
are no studies to show that it works in people who eat their normal diet.
Even so, Interneuron is a venture capital start up company, and the market
for diet aids in the U.S. is HUGE.

Fenfluramine does cause long-term 5-HT neuronal changes (in rats).  See a
paper by Johnson and Nichols, Pharmacology biochemistry and Behavior, Vol 36,
pp 105-109, 1990.  10 mg/kg of Dfen produced long-lasting changes.  A single
10 mg/kg dose of MDMA will not do this in rats.

Interestingly, although Dfen produces long-term deficits in brain levels of
5-HT, its metabolite 5-HIAA, and the biosynthetic enzyme tryptophan hydroxylase
as well as in the number of 5-HT uptake sites, Interneuron, and the French
parent company Servier claim that the neurons are "okay", they just don't have
any serotonin, any synthesis capacity, or the ability to take it up from the
synapse.  hmmm....  I guess you can't expect otherwise, or you'd be marketing
a diet aid that changed your brain structure, and you'd make no money on that.

By the way, studies of postmortem brains from auto accidents have shown that
while dopamine neurons decrease in number with age, serotonin neurons do not.
So the aging problem shifts the balance to serotonin and the loss of 5-HT
neurons while young may not show up later.  This may be a problem that only
really occurs with dopamine, which is pretty toxic stuff.

Of course we all know that amphetamine releases dopamine, and is a psycho-
stimulant, while fenfluramine, which releases 5-HT makes you feel full and
lethargic.  It makes you wonder about mental acuity in later years if the
serotonin system is there full-bore, but the dopaminergic system is dying!

Mon, 11 Nov 1996 14:13:10 GMT
 Pondimin (fenfluramine)


>This may be a problem that only
>really occurs with dopamine, which is pretty toxic stuff.

I wasn't aware of any excitotoxicity from dopamine itself.  The
neurotoxic effects of amphetamine are, I think, hypothesized to occur
from a metabolite of dopamine along a pathway that only becomes
significant when large amounts of it are{*filter*} around in the
synaptic cleft (e.g., from amphetamines).  I saw one article that
showed that OH-DOPA was not the excitotoxin in question (and can
dig it up on request).


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Tue, 12 Nov 1996 04:00:00 GMT
 [ 2 post ] 

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