D-1 and D-2 agonists in Parkinson's disease.

We have evaluated 5 DA agonists-bromocriptine, lergotrile, lisuride, pergolide, and mesulergine in studies encompassing 278 patients with advanced PD. In most of our patients the DA agonist was added to levodopa. Most of our patients were no longer satisfactorily responding to levodopa. Previous attempts at managing these patients by changing the dose of levodopa (increasing or decreasing it), the treatment schedule, or the ratio of levodopa to carbidopa or by temporarily discontinuing levodopa [drug holiday] were unsuccessful. The majority of our patients had diurnal fluctuations in performance, either "wearing off" or "on-off" phenomena. The addition of a DA agonist resulted in a decrease in parkinsonian disability in most patients and a decrease in the severity of the diurnal fluctuations in performance. Improvement in many patients was maintained for at least 2 years. Adverse effects included mental changes, dyskinesias, orthostatic hypotension, and nausea. All of the adverse effects were reversible when the agonist was decreased or discontinued. As a group the agonists behaved similarly but individual patients often responded better to one agonist than another. The main role of agonists is in combination with levodopa in the treatment of patients with early PD who have not yet developed dyskinesias or diurnal fluctuations in performance.