Adjuncts to levodopa therapy: dopamine agonists.

The classical role of dopamine agonists in Parkinson's disease (PD) therapy is adjunctive treatment to levodopa once "wearing-off" fluctuations or more malignant types of "on-off" swings have developed. Dopamine agonists reduce the frequency, severity, and duration of "off" periods while allowing the levodopa dose to be reduced. Interest is growing in the role of dopamine agonists as primary monotherapy in PD. Studies of early monotherapy have shown that, even with sustained treatment, drug-induced dyskinesias rarely develop. However, this approach is successful for more than 3 years in only about 30% of all PD patients. Continuous dopaminergic stimulation via subcutaneous dopamine agonist infusions is being investigated as a way to control levodopa-associated peak-dose dyskinesias. Early combined treatment with levodopa has been suggested as effective while avoiding long-term complications, but the therapy remains controversial. Despite the entry of several new dopamine agonists into clinical practice, the ideal agonist, with long duration of action and efficacy equal to that of levodopa, is still lacking. The clinical pharmacology of dopamine agonists is reviewed.