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A
review of the pharmacology of selegiline
J Knoll
Acta Neurol Scand
(Suppl.) Denmark 1991, 84/136 (44-59)
ABSTRACT
Selegiline (1-deprenyl) is an irreversible inhibitor of monoamine oxidase (MAO) type B.
Because in the human brain, dopamine is metabolised mainly by MAO-B, selegiline increases
dopamine content in the central nervous system. Besides the inhibition of MAO-B,
selegiline also inhibits the uptake of dopamine and noradrenaline into presynaptic nerve
and increases the turnover of dopamine. Thanks to these properties, selegiline
significantly potentiates the pharmacological effects of levodopa.
These favourable
characteristics have been applied in the treatment of Parkinson's disease using selegiline
both with levodopa and alone. Unlike earlier MAO-inhibitors, selegiline does not
potentiate the hypertensive effects of tyramine. This is due to the selectivity of MAO-B,
leaving intestinal MAO-A intact, and also due to the fact that selegiline inhibits the
uptake of tyramine into neurons. Selegiline can prevent the parkinsonism caused by MPTP in
animals; similar findings have been reported with other toxins like 6-OHDA and DSP-4, that
destroys noradrenergic nuclei. Furthermore, selegiline reduces oxidative stress caused by
degradation of dopamine and increases free radical elimination by enhancing superoxide
dismutase and catalase activity. These findings may be important when considering the
possible neuroprotective effects of selegiline. Besides the basic pharmacology also the
interactions and pharmacokinetics of selegiline are reviewed in this article.
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