Levodopa for the treatment of Parkinson’s disease: current perspectives

Abstract

Levodopa (LD) remains the most effective symptomatic treatment for Parkinson’s disease. Although it may be regarded as a replacement therapy, its mechanisms of action are complex and not completely understood. Chronic treatment with levodopa is associated with the appearance of motor and nonmotor complications in 40–80% of cases after 5–10 years of treatment, which are the major limitation of levodopa therapy. The age of onset of Parkinson’s disease, duration of levodopa treatment and daily dose of levodopa are the main risk factors for motor complications. The nonphysiological pulsatile stimulation of striatal dopamine receptors induced by periodic dosing of oral levodopa formulations may play a key role in the pathogenesis of motor fluctuations and dyskinesias. Although some concerns have been raised regarding a potential neurotoxic effect of levodopa, at present there is no clear evidence from basic and clinical studies that levodopa has an adverse effect on the progression of Parkinson’s disease.