Problems in patients with advancing Parkinson's disease

Aimsl-dopa remains the most effective treatment for Parkinson's disease. However, after a few years of l-dopa treatment, the drug often becomes less effective (wearing-off), and patients often manifest abnormal involuntary movements (dyskinesia). Moreover, long-term treatment with l-dopa produces psychiatric side effects. In advancing Parkinson's disease, patients also suffer from autonomic dysfunction. Thus, limitations remain with current antiparkinsonian therapy. This study summarizes the problems encountered during long-term treatment of Parkinson's disease.Methods and resultsThe symptoms in advancing Parkinson's disease are characterized by an oscillation of mobile and immobile states during long-term therapy with l-dopa. This situation is termed “on-off” phenomenon. There is no evidence that this phenomenon is induced by accumulation of l-dopa. How on-off phenomenon is induced remains unknown. Urinary urgency remains a common problem in parkinsonian patients. However, symptoms improve when agonist therapy is switched from bromocriptine (D2 agonist) to pergolide (D1 and D2 agonist). This has also been confirmed in animal models of parkinsonism using cynomolgus monkeys.ConclusionA variety of symptoms can manifest in patients with Parkinson's disease. Several symptoms can be improved by treatment with dopamine agonists, depending on the selective activation of a D1 or D2 receptor subtype.