From: gts (gts_2000@yahoo.com)
Date: Fri Feb 07 2003 - 01:21:23 MST
Rafal wrote:
>>gts wrote:
>>> As stated in the following abstract, from DATATOP, "The study found
>>> that deprenyl [selegiline] treatment almost halved the risk of
>>> reaching a stage of Parkinsonism at which the start of levodopa
>>> treatment becomes imperative for lessening disability."
>>> That looks like potent neuroprotection to me.
>
> >### It isn't. DATATOP found a *delay* in reaching the levodopa-requiring
> >level of symptomatology, not a reduction in total risk.
It has never been my claim that selegiline is a cure for the disease, Rafal.
There is no cure for PD. Selegiline is merely a treatment for it. Once
diagnosed correctly with PD, the risk of dying from PD related causes is
basically 100 percent. So yes, of course there is no reduction in "total
risk." But some studies do show an extension in lifespan in PD with
selegiline+levodopa vs levodopa alone.
Many, many dozens of published studies state, suggest, or offer evidence of
the neuroprotective value of selegiline in PD. I'm amazed that you have not
done more research in medline into this area. The DATATOP abstract itself
begins to discuss the possible means by which selegiline is neuroprotective,
(which I notice that you have conveniently ignored), but in any case DATATOP
is not the only data available. In some studies selegiline does in fact
extend lifespan in PD patients, and it's certainly already done so in lab
animals.
>>As background: there was once a hypothesis that levodopa accelerates the
>>attrition of dopaminergic neurons, and that levodopa-sparing therapy would
>>delay the onset of dyskinesias which usually develop after about 5-7 years
>>on levodopa, and perhaps prolong survival. A nice hypothesis, but not
>>true -substituting dopa-agonists or selegiline for levodopa in initial
treatment
>>does not delay the onset of dyskinesia. ...
I think are mistaken here to include selegiline in the same class of drugs
as levodopa. Levodopa is merely a simple dopamine agonist -- actually it's
not even that -- it's merely an ordinary amino acid and a precursor to
dopamine. Selegiline's actions are far more complex and less well
understood.
If you were really on top of this subject, Rafal, then I believe you and I
would not be arguing whether selegiline is neuroprotective. Instead we might
be arguing how and why it is neuroprotective. Several theories have been
advanced. For example it may protect neurons because it reduces the levels
of toxic by-products of MAO-B metabolism, or it may protect neurons because
it increases the levels of the natural antioxidants SOD and catalase. At
the moment I tend to support the latter theory.
Below is yet another published study about selegiline and neuroprotection.
In this abstract below, of a study published much more recently than
DATATOP, selegiline (deprenyl) was found to protect neurons from
free-radical damage in a dose dependent manner. It is suggested further that
the drug should be "applicable to delay the deterioration of neurons during
advancing aging..."
--- ABSTRACT: Neuroprotection by deprenyl and related compounds Maruyama W, Naoi M Department of Basic Gerontology, National Institute for Longevity Sciences Obu, Japan. maruyama@nils.go.jp Mech Ageing Dev 1999 Nov; 111(2-3):189-200 There is an increasing number of data by in vitro and in vivo experiments, indicating that (-)-deprenyl is neuroprotective to dopamine neurons, even though detailed mechanism remains to be clarified. In this paper neuroprotection by (-)-deprenyl and structurally related compounds was examined in concern with the suppression of apoptosis induced by a reactive oxygen species, peroxynitrite generated from SIN-1. The apoptotic DNA damage was quantitatively determined using dopaminergic SH-SYSY cells and by a single cell gel electrophoresis (comet) assay. DNA damage induced by peroxynitrite was proved to be apoptotic by prevention of the damage by cycloheximide or actinomycin-D. (-)-Deprenyl and other propargylamines protected the cells from apoptosis in a dose-dependent way. (-)-Deprenyl protected the cells even after it was washed out, suggesting that it may initiate the intracellular process to repress the apoptotic death program. The study on the structure-activity relationship of (-)-deprenyl analogues revealed that a N-propargyl residue with adequate size of hydrophobic structure is essentially required for the anti-apoptotic activity. These results suggest that (-)-deprenyl and related compounds may protect neurons from apoptosis and be applicable to delay the deterioration of neurons during advancing ageing and in neurodegenerative disorders. --- I have spent literally years of life studying and following this drug deprenyl (selegiline). I take a small dose of it every day, (with occasional two week breaks), for anti-aging purposes, much in the same way that I take my vitamins. I don't take prescription drugs lightly, but as someone interested in anti-aging via any means (chemical or otherwise) I can tell you that this drug is extremely interesting and very promising. The only public relations black-eye the drug has ever suffered occurred a few years ago, when an epidemiological study raised some concerns that adding selegiline to l-dopa might increase rather than decrease mortality rates in PD. However, as I've stated previously, subsequent metastudies have removed those concerns and restored selegiline to its rightful place in PD treatment. Other studies show that selegiline increases lifespan in animals as well as human PD patients. -gts
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