L-dopa therapy for Parkinson's disease: past, present, and future.

Dopamine (DA) supplementation therapy by l-dopa for Parkinson's disease (PD) was established around 1970. The dose of l-dopa can be reduced by the combined administration of inhibitors of peripheral l-amino acid decarboxylase (AADC), catechol O-methyltransferase (COMT), or monoamine oxidase B (MAO B). DA in the striatum may be produced from exogenously administered l-dopa by various AADC-containing cells, such as serotonin neurons. The long-term administration of l-dopa in PD patients may produce l-dopa-induced dyskinesia (LID), which may be due to chronic overstimulation of supersensitive DA D1 receptors. l-dopa may be used in combination with various new strategies such as gene therapy or transplantation in the future.