Selegiline inhibits the activity of
monoamine oxidase B, enhances the release of
dopamine, blocks the uptake of
dopamine, acts as a
calmodulin antagonist, and enhances the level of
cyclic AMP, which in turn protects dopaminergic neurons. It possesses cognition-enhancing functions, rejuvenates serum
insulin-like growth factor I in aged rats, and enhances life expectancy in rodents.
Selegiline possesses neurotrophic-like actions, and rescues axotomized motorneurons independent of
monoamine oxidase B inhibition. It enhances the synthesis of
nerve growth factor, protects dopaminergic neurons from
glutamate-mediated neurotoxicity, and protects dopaminergic neurons from toxic factors present in the spinal fluid of parkinsonian patients, and the said effect may be mediated via elaborating
brain derived neurotrophic factor.
Selegiline increases the striatal
superoxide dismutase, protects against
peroxynitrite- and
nitric oxide-induced apoptosis, and guards dopaminergic neurons from toxicity induced by
glutathione depletion. It stimulates the biosynthesis of
interleukin 1-beta and
interleukin-6, is an immunoenhancing substance, possesses antiapoptotic actions, and is
neuroprotectant in nature.
Selegiline has been shown to be efficacious in
Parkinson's disease, global
ischemia, Gille de la
Tourette syndrome, and
narcolepsy. Its therapeutic efficacy in
Alzheimer's disease remains uncertain. In
Alzheimer's disease, short term studies of
selegiline suggest a beneficial effect; whereas long term studies are less convincing.