Clinical pharmacology of dopamine agonists in Parkinson's disease.

Oral levodopa is the most effective symptomatic treatment for Parkinson's disease. Dopamine agonists are useful adjuvants to levodopa in the pharmacotherapy of parkinsonian patients. Monotherapy with dopamine agonists in early Parkinson's disease has been advocated in order to delay the occurrence of complications associated with long term administration of levodopa. The use of dopamine agonists alone provides an adequate antiparkinsonian effect in only a minority of patients. In early stages of Parkinson's disease, dopamine agonists can produce a clinical response comparable with levodopa but, thereafter, their efficacy wanes. Early initiation of combination therapy with levodopa and dopamine agonists appears to reduce the severity and delay the appearance of the complications associated with long term administration of levodopa. Currently, dopamine agonists are most commonly used in combination with levodopa in patients in advanced stages of the disease who experience fluctuations of their motor symptoms. Despite their different pharmacodynamic and pharmacokinetic profiles, the ergot derivatives bromocriptine, lisuride and pergolide appear to be very similar in terms of their clinical efficacy. Continuous dopaminergic stimulation by parenteral infusion of water-soluble dopamine agonists such as apomorphine and lisuride can overcome motor fluctuations in advanced Parkinson's disease. Other dopamine agonists such as cabergoline, pramipexole and ropinirole are currently being studied. Further studies with these compounds will be required to determine their efficacy and adverse effects in comparison with the currently available orally active ergot agonists. It has been suggested that oxidative stress resulting from dopamine metabolism may be reduced by the administration of dopamine agonists. These drugs may therefore slow the rate of progression of Parkinson's disease. At present, however, there is no convincing clinical data to support a neuroprotective effect of dopamine agonists.