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The following message was posted to: PharmPK
I need a little help with this question.
Buscolysin is a quaternary amine form of scopolamine,
and as such (carrying a positive charge) it should not
cross the blood brain barrier. Scopolamine, a
tertiary and neutral amine, does cross quite well.
Does anyone know how it might be possible to take oral
Buscolysin and still have it exert CNS toxicity?
Concomitant administration of other drugs, metabolic
states, etc.
One "theory" I had is that perhaps the body
metabolizes Buscolysin (N-butyl scopolammonium, or
scopolamine butylbromide) into something that does
penetrate the CNS, and could cause toxicity? But I
have not been able to figure out what the metabolites
are. This may be the way to go.
It is an odd question, I realize, but it apparently
happened and I am now charged with understanding how
it occurred.
Any help you can give me would be very appreciated.
AO
achillesoutlaw.aaa.yahoo.com
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The following message was posted to: PharmPK
Hi Achilles,
by pure chance I found a hint, which might help to solve your problem:
Science Vol 290, 2000, page 1068:
Pesticide Causes Parkinsons's in Rats: [...] "MPTP is metabolized to MPP+,
which slips through the blood-brain barrier"
MPP+ =3D N-Methyl-4-phenylpyridinium <-- cationic
MTPT =3D 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
I don't think that the metabolism MTPT --> MPP+ happens in the brain, so I
conclude, that it is possible for some cationic compounds to penetrate the
blood-brain-barrier.
Be aware: MTPT is a commonly used abbreviations with a lot of very different
meanings
Best regards
Joerg
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No this is not correct. MPTP is not a pesticide to start with. But MPTP
crosses the BBB, where it is metabolized by monamine oxidase in the brain to
form the toxic MPP+.
Dale Sharp
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For review of organic cation transporters and other transporters in the
brain see: J. Pharm. Sci. 89, 1371-1388, 2000.
Bernhard J. Ladstetter, Ph.D.
Institute of Pharmacokinetics and Metabolism
Merck KGaA
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The following message was posted to: PharmPK
MPTP is metabolized to MPP+ in the brain after MPTP crosses through the BBB.
This concept was extensively studied by Nick Bodor's group at Univ. of
Florida with similar compounds (the phenyl group was at the 3 position) and
he has published quite a few papers on the subject. He was attempting to use
this technique to deliver drugs to the brain and retain them in the brain.
Incidentally, as I remember it (not quite sure) the Parkinsonism caused by
MPTP in rodents is reversible after a few hours. The primate on the other
hand shows a condition that is similar to humans and is irreversible.
Anup Zutshi Ph.D.
Pharmacokinetics and Metabolism
Pharmaceutical Product Development
Battelle Memorial Institute
Tel.No: (614) 424-5997
Fax: (614) 424-3268
E-Mail: zutshi.-at-.battelle.org
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