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- Path: sparky!uunet!destroyer!ncar!hsdndev!spdcc!dyer
- From: dyer@spdcc.com (Steve Dyer)
- Newsgroups: sci.med
- Subject: Re: Deprenyl
- Message-ID: <1992Nov17.181034.13282@spdcc.com>
- Date: 17 Nov 92 18:10:34 GMT
- References: <1992Nov16.235730.2369@cnsvax.uwec.edu>
- Organization: S.P. Dyer Computer Consulting, Cambridge MA
- Lines: 45
-
- In article <1992Nov16.235730.2369@cnsvax.uwec.edu> nyeda@cnsvax.uwec.edu (David Nye) writes:
- >Deprenyl is an irreversible inhibitor of MAO-B purported to slow the
- >progression of Parkinson's disease. It as been in use in Europe for
- >many years as an adjunct in the symptomatic treatment of PD. The
- >Europeans have, I am told, not been terribly excited about the drug.
- >The studies that have purported to show slowing of the progression of
- >the disease have methodological problems. It is usually given twice
- >a day. A month's worth costs around $100.
-
- Isn't there an ongoing study (whatitsname? DATATOP?) which is looking
- at the efficacy of l-deprenyl (selegiline) and Vitamin E in slowing the
- progression of the disease? I understood that intermediate analysis of
- the data showed a modest difference in the selegiline group, but that
- it wasn't obvious yet whether this was due to a therapeutic effect as
- opposed to a disease-modifying effect. Gordon is probably undoubtedly
- more up to date on this than I would ever be.
-
- >My question/suggestion: since it irreversibly inhibits MAO-B and has
- >a half life of well over a month, why not give only two tablets a
- >month? That is, presuming that one thinks it should be given at all
- >if it's efficacy hasn't been proven conclusively. It sure would be a
- >heck of a lot cheaper. Thoughts?
-
- There are a couple of issues here. _Which_ has a 1/2 life of over a
- month? MAO-B? I'm pretty sure that selegiline is metabolized and
- excreted much more quickly. Still, it is common even in antidepressant
- therapy with non-specific MAOIs to give the drug daily. MAO inhibition
- increases over time, and is rarely complete with daily dosing, and of
- course, the enzyme is being continually resynthesized. According to
- Bob Yazz, one or two tablets a month is part of the Durk 'n Sandy Shaw
- (Life Extension) recipe for a longer life (for what that's worth!)
-
- One issue with selegiline is that it is metabolized to l-methamphetamine
- and l-amphetamine, both of which achieve significant levels, and these
- both have effects on dopamine reuptake and release. So, it's hard to
- separate any l-DOPA-sparing effects due to its MAO inhibition from the
- effects mediated by the amphetamines from the long-term effects
- mediated (possibly) by slowing the oxidation of MAO-B substrates which
- are converted to neurotoxic substances. Maybe selegiline has a modest
- acute effect, but its protective effects could be evidenced by less
- frequent dosing? I don't think we really know yet!
-
- --
- Steve Dyer
- dyer@ursa-major.spdcc.com aka {ima,harvard,rayssd,linus,m2c}!spdcc!dyer
-