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National Institute for
Longevity Sciences, 36-3, Gengo, Morioka-cho, Obu-shi,
Aichi 474-8522, Japan.
(--)Deprenyl, a monoamine oxidase
B (MAO B) inhibitor is known to upregulate activities
of anti-oxidant enzymes such as superoxide dismutase
(SOD) and catalase (CAT) in brain dopaminergic regions.
The drug is also the sole chemical which has been
repeatedly shown to increase life spans of several
animal species including rats, mice, hamsters and
dogs. Further, the drug was recently found to enhance
anti-oxidant enzyme activities not only in brain dopaminergic
regions but also in extra-brain tissues such as the
heart, kidneys, adrenal glands and the spleen. We
and others have also observed mobilization of many
humoral factors (interferone (INF)-gamma, tumor necrosis
factor (TNF)-alpha, interleukine (IL)-1beta,2,6, trophic
factors, etc.) and enhancement of natural killer (NK)
cell functions by (-)Deprenyl administration. An apparent
extension of life spans of experimental animals reported
in the past may be better explained by these new observations
that (-)Deprenyl upregulate SOD and CAT activities
not only in the brain but also in extra-brain vital
organs and involve anti-tumorigenic as well as immunomodulatory
effect as well. These combined drug effects may lead
to the protection of the homeostatic regulations of
the neuro-immuno-endocrine axis of an organism against
aging.
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University of Rochester
Medical Center, Rochester, NY 14620, USA.
Deprenyl (selegiline) delays the
need for levodopa therapy in patients with early Parkinson's
disease, but the long-term benefits of this treatment
remain unclear. During 1987 to 1988, 800 patients
with early Parkinson's disease were randomized in
the Deprenyl and Tocopherol Antioxidative Therapy
of Parkinsonism trial to receive Deprenyl, tocopherol,
combined treatments, or a placebo and were then placed
on active Deprenyl (10mg/day). A second, independent
randomization was carried out in early 1993 for 368
subjects who by that time had required levodopa and
who had consented to continuing the Deprenyl treatment
(D subjects) or changing to a matching placebo (P
subjects) under double-blind conditions. The first
development of wearing off, dyskinesias, or on-off
motor fluctuations was the prespecified primary outcome
measure. During the average 2-year follow-up, there
were no differences between the treatment groups with
respect to the primary outcome measure (hazard ratio,
0.87; 95% confidence interval, 0.63, 1.19; p = 0.38),
withdrawal from the study, death, or adverse events.
Although 34% of D subjects developed dyskinesias and
only 19% of P subjects did (p = 0.006), only 16% of
D subjects developed freezing of gait but 29% of P
subjects did (p = 0.0003). Decline in motor performance
was less in D subjects than P subjects. Levodopa-treated
Parkinson's disease patients who had been treated
with Deprenyl for up to 7 years, compared with patients
who were changed to a placebo after about 5 years,
experienced slower motor decline and were more likely
to develop dyskinesias but less likely to develop
freezing of gait.
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