Parkinson's disease, known also as striatal dopamine deficiency syndro
me, is a degenerative disorder of the central nervous system character
ized by akinesia, muscular rigidity, tremor at rest, and postural abno
rmalities. In early stages of parkinsonism, there appears to be a comp
ensatory increase in the number of dopamine receptors to accommodate t
he initial loss of dopamine neurons. As the disease progresses, the nu
mber of dopamine receptors decreases, apparently due to the concomitan
t degeneration of dopamine target sites on striatal neurons. The loss
of dopaminergic neurons in Parkinson's disease results in enhanced met
abolism of dopamine, augmenting the formation of H2O3, thus leading to
generation of highly neurotoxic hydroxyl radicals (OH .). The generat
ion of free radicals can also be produced by 6-hydroxydopamine or MPTP
which destroys striatal dopaminergic neurons causing parkinsonism in
experimental animals as well as human beings. Studies of the substanti
a nigra after death in Parkinson's disease have suggested the presence
of oxidative stress and depletion of reduced glutathione; a high leve
l of total iron with reduced level of ferritin; and deficiency of mito
chondrial complex I. New approaches designed to attenuate the effects
of oxidative stress and to provide neuroprotection of striatal dopamin
ergic neurons in Parkinson's disease include blocking dopamine transpo
rter by mazindol, blocking NMDA receptors by dizocilpine maleate, enha
ncing the survival of neurons by giving brain-derived neurotrophic fac
tors, providing antioxidants such as vitamin E, or inhibiting monoamin
e oxidase B (MAO-B) by selegiline. Among all of these experimental the
rapeutic refinements, the use of selegiline has been most successful i
n that it has been shown that selegiline may have a neurotrophic facto
r-like action rescuing striatal neurons and prolonging the survival of
patients with Parkinson's disease.