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

Abstract 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.