For over 30 years, levodopa has been the gold standard for managing the sym
ptoms of Parkinson's disease. Treatment with levodopa has resulted in a mar
ked decrease in disease-associated mortality and morbidity. However, one of
its drawbacks is that many patients experience a shorter duration of respo
nse and increased motor fluctuations with disease progression and longterm
levodopa therapy. These increased motor fluctuations, including dyskinesias
, may be the consequence of oxidative stress or inability to store and regu
late intrasynaptic dopamine concentrations with disease progression. Clinic
al investigations have demonstrated that continuous dopaminergic stimulatio
n may widen the therapeutic window for levodopa and improve motor fluctuati
ons. Strategies for providing continuous dopaminergic replacement include a
dministration of levodopa by continuous infusion, controlled-release levodo
pa, long-acting dopamine agonists, and inhibitors of levodopa metabolism. T
he catechol-O-methyltransferase inhibitors that block a compensatory metabo
lic pathway for levodopa and prolong its duration may improve the consisten
cy of the dopaminergic response.