Management of motor fluctuations in Parkinson's disease.

A complication of chronic levodopa therapy is a shortening of benefit of each dose. Peripheral pharmacokinetics, central pharmacokinetics, and central pharmacodynamics are involved in the pathophysiology of motor fluctuations. Strategies to improve 'wearing-off' fluctuations attempt to provide more constant plasma levodopa levels or more continuous stimulation of dopamine receptors. Controlled-release levodopa preparations are very effective for mild to moderate fluctuations. The addition of direct-acting dopamine agonists or the MAO-B inhibitor selegiline is helpful for short-term improvement. Liquid levodopa is beneficial for some patients with severe fluctuations. Apomorphine injections will provide immediate 'rescue' from 'off' states. Catechol-O-methyl transferase inhibitors are a new class of drugs which appear to improve motor fluctuations. Manipulations of dieting protein may reduce fluctuations in some patients. It is possible that motor fluctuations may be delayed by the early use of sustained release levodopa preparations or early combinations of levodopa with a dopamine agonist.