Anti-parkinsonian drugs today

The drug treatment of Parkinson's disease has progressed through 3 main stages: firstly, the use of anticholinergic drugs and amantadine; then the introduction of levodopa and its association with peripheral decarboxylase inhibitors; and finally the use of direct acting dopamine agonist drugs. Levodopa, however, remains the most effective single drug in Parkinson's disease. Unfortunately, the side effects associated with long term levodopa treatment today constitute an important cause of functional disability. 'Positive' side effects such as involuntary movements and psychiatric disorder remain difficult to manage without causing an increase in Parkinsonian immobility; conversely, management of the 'negative' phenomenon of the 'off' period is limited by these same side effects. This has generated renewed interest in the highly complex pharmacokinetic and pharmacodynamic properties of levodopa, with the aim of reducing fluctuations in plasma levodopa (and hence brain dopamine) concentrations by sustained release oral or continuous parenteral administration of the drug.