Levodopa in Parkinson's disease: from the past to the future

Importance of the field: Levodopa is the mainstay of symptomatic treatment for Parkinson's disease (PD). Although other treatments have been developed in the last 30 years, most patients use levodopa in view of its superior efficacy in controlling PD symptoms. Unfortunately, levodopa is associated with long-term motor complications (motor fluctuations and dyskinesias). The main causes of these undesirable effects are the narrowing of the therapeutic window with the natural progression of the disease, pulsatile dopaminergic stimulation due to the short half-life of the drug and erratic absorption. Several studies suggest that PD control could be enhanced by changing the mode of levodopa delivery so as to ensure continuous and stable supply of the drug to the brain. The objective of this text is to review the ascertained strengths and limitations of levodopa in PD, starting from its history, and propose novel modes of usage designed to cover currently unmet medical needs.Areas covered in this review: Medline literature search (from 1973 to date).What the reader will gain: A perspective on the evolution of PD pharmacological treatment.Take home message: Levodopa still is the best treatment for PD. Truly stable and controlled formulations that ensure clinical response should be developed to reduce the undesirable effects that restrict its efficacy.