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National Institute for Longevity
Sciences, 36-3, Gengo, Morioka-cho, Obu-shi, Aichi 474-8522,
Japan. kitani@nils.go.jp
(--)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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