From: Rafal Smigrodzki (rms2g@virginia.edu)
Date: Mon Jan 27 2003 - 17:24:31 MST
gts wrote:
I also
> recommend vinpocetine, (which increases glucose utilization in the
> brain), and of course ginkgo biloba.
>
> Another compound of interest is deprenyl, aka selegiline
> hydrochloride. This is a prescription drug used in the treatment of
> Parkinson's disease. I personally take 5 mg of deprenyl daily, though
> I do not suffer from Parkinson's. Deprenyl protects the dopamine
> producing cells of the substantia nigra, and seems to enhance mental
> acuity as well. Deprenyl also enhances production of the natural
> anti-oxidants SOD and Catalase, both of which are associated with
> increased longevity in animal studies.
>
### There have been recently some studies showing no improvement in disease
progression in PD patients on selegiline, as well as negative results with
gingko extracts.
Here are some reviews about selegiline:
Selegiline: a second look. Six years later: too risky in Parkinson's
disease.
Prescrire International. 11(60):108-11, 2002 Aug.
Abstract
(1) The reference treatment for Parkinson's disease is levodopa plus a
peripheral dopadecarboxylase inhibitor (benserazide or carbidopa). (2) In
1996, selegiline, a type B MAOI marketed in France since 1988, saw its
indications extended to cover single-agent therapy of early-stage
Parkinson's disease, and in combination with levodopa, before onset of
complications of levodopa therapy. The initial clinical file failed to show
that selegiline had any benefit in these indications. (3) Now, in 2002, new
data from trials involving hundreds of untreated patients show that
selegiline postpones the need for levodopa therapy for a few months but
fails to substantially alter the progression of Parkinson's disease. (4) A
clinical trial and a retrospective epidemiological study of patients with
advanced Parkinson's disease showed excess mortality on selegiline. (5) The
side effects of selegiline are similar to those of other antiparkinsonian
drugs and amphetamine. Notable side effects include cardiovascular problems
(postural hypotension, atrial fibrillation and arterial hypertension). (6)
Selegiline can cause a serotoninergic syndrome and arterial hypertension, so
must not be combined with pethidine, tramadol, bupropion, sumatriptan,
zolmitriptan or naratriptan. Concurrent treatment with serotonin reuptake
inhibitor antidepressants should also be avoided. (7) Given the only
moderate effects of selegiline in Parkinson's disease, and the possibility
of a slight increase in mortality, there is no justification for prescribing
this medication in patients with Parkinson's disease. (8) Whatever the stage
of Parkinson's disease, there is no justification for starting patients on
selegiline. Patients who are already taking selegiline should only continue
to take it if they feel a clear benefit and are free from risk factors for
early mortality, especially cardiovascular disease
------------------
Ebadi M. Sharma S. Shavali S. El Refaey H.
Neuroprotective actions of selegiline.
Journal of Neuroscience Research. 67(3):285-9, 2002 Feb 1.
Abstract
Selegiline, a selective inhibitor of monoamine oxidase-B (MAO-B), was one of
the first adjunct therapies in clinical neurology. A retrospective analysis
of data from patients with Parkinson's disease found a significant increase
in survival in those treated with selegiline plus L-dopa compared with
L-dopa alone. The mechanism of action of selegiline is complex and cannot be
explained solely by its MAO-B inhibitory action. Pretreatment with
selegiline can protect neurons against a variety of neurotoxins, such as
1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP), 6-hydroxydopamine,
N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4),
methyl-beta-acetoxyethyl-2-chloroethylamine (AF64A), and
5,6-dihydroxyserotonin, which damage dopaminergic, adrenergic, cholinergic,
and sertoninergic neurons, respectively. Selegiline produces an
amphetamine-like effect, enhances the release of dopamine, and blocks the
reuptake of dopamine. It stimulates gene expression of L-aromatic amino acid
decarboxylase, increases striatal phenylethylamine levels, and activates
dopamine receptors. Selegiline reduces the production of oxidative radicals,
up-regulates superoxide dismutase and catalase, and suppresses nonenzymatic
and iron-catalyzed autooxidation of dopamine. Selegiline compensates for
loss of target-derived trophic support, delays apoptosis in serum-deprived
cells, and blocks apoptosis-related fall in the mitochondrial membrane
potential. Most of the aforementioned properties occur independently of
selegiline's efficacy to inhibit MAO-B. Copyright 2002 Wiley-Liss, Inc.
[References: 36
-----------------
Wilcock GK. Birks J. Whitehead A. Evans SJ.
The effect of selegiline in the treatment of people with Alzheimer's
disease: a meta-analysis of published trials.
ACP J Club. 2002 Jul-Aug;137(1):10; PMID: 12093209, Comment in: Evid Based
Ment Health. 2002 Aug;5(3):88; PMID: 12180455
International Journal of Geriatric Psychiatry. 17(2):175-83, 2002 Feb.
Abstract
OBJECTIVE: To evaluate the effect of selegiline in the treatment of patients
with Alzheimer's disease, in terms of cognitive performance, functional
ability, emotional state (including behaviour and mood) and global response.
Data Sources The Cochrane database of trials, Embase, Medline and Psychlit.
Study Selection Unconfounded, double-blind, randomised trials of selegiline
compared with placebo reported before 31 December 1998. Data Extraction The
reviewers selected trials for inclusion. Individual patient data were
sought, but when these could not be retrieved summary data were extracted
from published papers. RESULTS: Of 27 identified trials, 14 met the
inclusion criteria. Individual patient data were retrieved from eight trials
on 821 patients. Summary data were extracted from five trials on 240
patients. No data were available from one trial on 12 patients, which was
therefore excluded from the meta-analysis. Fixed and random effects
meta-analyses were performed on standardised mean differences. For cognition
there was a statistically significant difference between selegiline and
placebo at 4-6 weeks and 8-17 weeks after randomisation (at 8-17 weeks:
smd=0.45 [95% confidence interval 0.03 to 0.88]), but this disappeared at
later assessments. The size of the treatment difference was considered
unlikely to be of clinical importance. Although there was a statistically
significant difference at 4-6 weeks for activities of daily living, this
disappeared at later assessments (at 8-17 weeks: smd=0.33 dot - black
diamond with white center dot - dot -]; [- dot - black diamond with white
center dot - dot -]0.33, 0.69]). There were no statistically significant
differences or clinically relevant differences between selegiline and
placebo in terms of emotional state or global response. CONCLUSION: Although
there was some evidence of improvement with selegiline in the short term in
cognition and activities of daily living, the magnitude of the effect did
not reach clinical importance. There was no evidence of long term effects.
Copyright 2002 John Wiley & Sons, Ltd
### The data are largely inconclusive, with the studies most favorable to
selegiline being criticized for methodological failings. Coupled with the
high cost of Deprenyl, this makes the case for its use quite shaky.
If I may tout my own prescription for a long life of agile thinking:
statins.
Unequivocally shown to prolong survival in patients with atherosclerosis
(meaning most of us after age 50 or so), now implicated in a possible
protective effect on Alzheimer's disease (in observational studies only).
Rafal
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