Hatton at Ifn-magdeburg.de
Wed Nov 20 21:58:08 EST 1996
> In article <Pine.LNX.3.95.961117201558.24859A-100000 at shell1.erols.com> DR JERRY CHANDLER <jlrchand at erols.com> writes:
> >From: DR JERRY CHANDLER <jlrchand at erols.com>
> >Subject: Re: Parkinsons-Pesticides
> >Date: Sun, 17 Nov 1996 20:21:48 -0500
> >If my memory serves me correctly, two chemical agents - paraquat and
> >diquat - may be of interest to you. Perhaps this effect was discovered
> >among illicit drug users who inhaled significant quantities of these
> >agents. Discovery of these agents started a flood of research on the
> >mechanism of action and the disease - genesis processes.
> >I would assume that any recent toxicology text or Toxline would provide
> >further information.
> >If further help is urgently needed, you can call me at the number given
> I have a vague memory of a biochemistry seminar where it was pointed out that
> a contaminant in designer drugs caused parkinson-like symptoms. It worked by
> inactivating mitochondria, those in one particular part of the brain were
> particularly susceptible. It's quite possible that a pesticide could have the
> same effect, though someone would have to have looked for it.
I also remember from a not so distant Toxicology lecture, something
similiar, so I delved into my notes and Leonard's Fundamentals of
Psycopharmacology(1992) and Timbrells "Principals of Biochemical
n-methyl-4-phenyl-pyridinium, is the contaminate and the metabolite MPP+
is the neurotoxin and destroys dopamine preoducing cells. Leonard
speculates that herbicides may produce the same symptoms. I myself
would go along with that and now I would sugges that metabolites in
small concetration would cross blood brain barrier after
biotransformation by Cyto. P450's on the endothelia cells. (haven't any
except that Paraquat is a bipyridylium compound, toxic in the lung
principally probably therfore metabolised similarly.
Also that it uses the polyamine uptake system for putrescine and
spermine, It is most toxic when bound to the redox NADP+ /NADPH cycle
producing lots of superoxide and depleting glutathione levels.
If anybody want to other me a job/studentship in this area, I be most
interested, because many "pesticides" induce Cyto. P450 expression, not
just in the liver, but lung and brain also. I've loads of ideas, but
they fall on deaf ears here.
Institute for Neurobiology
Is life just a game where we make up the rules while we are searching
for something to say, or are we just simply spirals of self replicating
(Monty Python- from the meaning of life).
Please note that the above views are my own and not (just) those of the
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