Re: MAPS: fenfluramine vs MDMA neurotoxicity

[Jon Freedlander <jfreed1@xxxxxxxx>]

On Sat, 9 Feb 2002, Alex Gamma wrote:

> Dear Forum, Matt, Ilsa,
>
> It is known that fenfluramine is about two (or even more) times as
> neurotoxic as MDMA in animals, but I can't seem to find any really good
> references for this fact. Can anybody help me? It seems to me that there
> once was a paper that specifically dealt with this comparison. Any help
> would be appreciated!

the following sounds about like what you're looking for; i don't have the
full text right now, but i could hunt around for it a bit if you like =)

Ann N Y Acad Sci 1990;600:649-61; discussion 661-4

Neurotoxicity of MDMA and related compounds: anatomic studies.

Molliver ME, Berger UV, Mamounas LA, Molliver DC, O'Hearn E, Wilson MA.

Department of Neuroscience, Johns Hopkins University School of Medicine,
Baltimore, Maryland 21205.

	The cytotoxic effects of amphetamine derivatives were studied by
immunocytochemistry to identify the cellular compartments affected by these
drugs, to obtain morphologic evidence of neuronal degeneration, and to assess
the potential for regeneration. The substituted amphetamines, MDA, MDMA, PCA,
and fenfluramine, all release serotonin and cause acute depletion of 5-HT from
most axon terminals in forebrain. (1) Unequivocal signs of axon degeneration
were seen at 36-48 hour survivals: 5-HT axons exhibited increased caliber,
huge, swollen varicosities, fragmentation, and dilated proximal axon stumps.
(2) Fine 5-HT axon terminals were persistently lost after drug administration,
while beaded axons and raphe cell bodies were spared. These two types of 5-HT
axons, which arise from separate raphe nuclei and form distinct ascending
projections, are differentially vulnerable to psychotropic drugs. (3) From 2-8
months after treatment, there was progressive serotonergic re-innervation of
neocortex along a fronto-occipital gradient. Longitudinal 5-HT axons grew
into layers I and VI from rostral to caudal, before sprouting into middle
cortical layers; this bilaminar pattern of growth simulates perinatal
development of 5-HT innervation. This study demonstrates differential
vulnerability of 5-HT projections, evidence for axonal degeneration, and
sprouting of 5-HT axons leading to re-innervation of forebrain. While the
sprouting axons are anatomically similar to the type that was damaged,
it is not known whether a normal pattern of innervation is re-established.

Publication Types:
Review
Review, Tutorial

PMID: 1979216 [PubMed - indexed for MEDLINE]

_______________________________________________________________________________
Jon Freedlander
Research Assistant
Multidisciplinary Association for Psychedelic Studies
www.maps.org

"Wisdom cannot be transmitted, it keeps you hanging on..."
							--Robyn Hitchcock



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