Problems with current pharmacologic treatment of Parkinson's disease.

For the past 30 years levodopa (LD) has been the pharmacologic standard of care for treating idiopathic parkinsonism (Parkinson's disease or PD), a neurodegenerative disease of the central nervous system. LD is a pharmacologically inactive precursor, which is converted enzymatically to the neurotransmitter dopamine by a declining population of neurons in the substantia nigra, the most important site of the pathology of PD. Most patients experience a smooth, lasting response to small amounts of LD during the early years of treatment, but as the underlying disease gets worse, treatment-related problems arise. Motor fluctuations, which slowly emerge after 3-5 years of chronic LD therapy, gradually replace the smooth pattern of response, and more frequent dosing is required. Abnormal involuntary movements (dyskinesia), wearing-off of the motor response after a few hours, organic psychosis (confusion and hallucinations), and progressive loss of independence characterize the complicated interaction between the drug and the disease. Despite its problems, including the theoretical potential for harming neurons by inducing oxidant stress, and the recent development of other antiparkinson drugs, LD remains the most effective pharmacologic agent available for the relief of symptoms in patients with PD.