From: dyer@spdcc.com (Steve Dyer)
Subject: Re: Deprenyl info wanted
Keywords: hemp, marijuana, prohibition
Organization: S.P. Dyer Computer Consulting, Cambridge MA
Date: Thu, 9 Apr 1992 00:55:55 GMT

In article <1468@celia.UUCP> celia!gray@usc.edu (Steve Gray) writes:
>Anyone have any info on Deprenyl?  I came across it in a catalog from
>Pharmaceuticals International.  They claim it can have similar effects to
>Prozac.  Ideas on safe dosages?  Is it contra-indicated in any cases?
>Also, what is it really?  The name "Deprenyl" does not show up in any of the
>indicies in a (1990) PDR.

The official nonproprietary name in the US is "selegiline", and it's
sold in the US under the tradename "Eldepryl".  It is approved in the
US as an adjunctive medication for the treatment of Parkinson's
disease.  There is some evidence that it not only has a mild acute
beneficial effect in potentiating l-DOPA, the primary therapeutic agent
used to treat Parkinsonism, but that it may also slow the (heretofore
inexorable) progression of the disease.

Deprenyl is a derivative of levo-methamphetamine (the stuff in Vicks
Inhalers, not the dextro- isomer, which is a more potent and powerful
central stimulant.)  Specifically, deprenyl is levo-N-propargyl-meth-
amphetamine.  The N-propargyl group, with its energetic acetylenic
carbon-carbon triple bond, yields an irreversible MAO inhibitor, but
one with some unique properties.

MAO inhibitors are used therapeutically in the treatment of depression.
By inhibiting the breakdown of catecholamines and serotonin via MAO,
and producing acutely an relative accumulation of these substances,
over time with long term exposure, they cause long-term changes in
neurotransmitter receptor populations which appear to be related to
their antidepressant effects.  Now, all antidepressant MAOIs are
irreversible, like deprenyl, but they also are unselective:  they
inhibit two subtypes of MAO, MAO-A and MAO-B identically.  MAO-A is
found in the brain, gut, liver, and platelets, and is involved
primarily with the destruction of norepinephrine, serotonin and
catecholamine-like substances found in foods.  As many of you know,
some foods (aged cheeses, vegemite, certain wines like chianti, fava
beans--shades of Hannibal Lecter!) contain tyramine, formed from the
breakdown of the amino acid tyrosine.  In normal individuals, tyramine
is destroyed by MAO in the gut and liver, so that it is essentially
without effect.  Individuals given MAOIs, however, absorb tyramine, and
it releases stored catecholamines from synapses in the peripheral
nervous system, causing a rapid rise in blood pressure, headaches, and
sometimes a stroke or death.  Bad news.  Sympathomimetic amines like
phenylpropanolamine and ephedrine, which are ubiquitous in allergy and
cold medications, have similar drug interactions.

Now, deprenyl is unusual.  It appears to be relatively selective for
MAO-B, and inhibits MAO-A only at higher doses.  MAO-B is involved in
the metabolism of dopamine, the neurotransmitter which is in deficit in
Parkinson's patients.  People given low doses of deprenyl (5-15mg/day)
show an almost complete inhibition of MAO-B, but little effect on
MAO-A.  This means, among other things, that at such doses, careful
dietary restriction doesn't seem to be necessary.  At higher doses
(30-60mg/day), deprenyl seems to lose its selectivity, and inhibits
MAO-A and MAO-B.  While it hasn't been associated with "cheese
reactions" at these higher doses, this may simply reflect its usage
pattern.  Experimental infusions of tyramine do produce increases in blood
pressure when high doses of deprenyl are administered, so the potential
for such adverse reactions is still there.  

Deprenyl is metabolized to levomethamphetamine and levoamphetamine,
but it's not clear yet what role (if any) these metabolites play in
its actions.  The drug does not appear to be a potent stimulant.
That is, it does not produce amphetamine-like subjective effects.
It also appears to be unimpressive as an antidepressant compared
to the unselective MAO inhibitors.  It shows some antidepressant
activity when given at higher doses when it becomes unselective.
At such doses, it may not have an advantage over the established
MAOIs.

The recent interest in the drug comes from its promotion as an
"anti-aging" drug, not the least by Joseph Knoll, its Hungarian
inventor.  It is true that some animals given deprenyl chronically
live longer than control animals, and it appears that Parkinsonism
patients on the drug live longer than those who aren't given it
(but then, the progression of Parkinsonism shortens life anyway).
Whether that means that it's good to self-medicate with it, in the
great tradition of alt.psychoactives, is quite a different matter.

-- 
Steve Dyer
dyer@ursa-major.spdcc.com aka {ima,harvard,rayssd,linus,m2c}!spdcc!dyer