A rationale for dopamine agonists as primary therapy for Parkinson's disease

Levodopa is the most potent symptomatic treatment for Parkinson's disease but adverse reactions are common and the initial response is not maintained. Further there is recent evidence that suggests that free radicals generated from the oxidative metabolism of dopamine may contribute to the pathogenesis of Parkinson's disease. This raises the possibility that levodopa therapy by way of its conversion to dopamine may promote free radical formation and accelerate the rate of neuronal damage. Levodopa sparing strategies designed to minimize the cumulative levodopa dosage employed over the course of the disease seem a rational way to treat Parkinson patients in face of current information. Such a strategy would include the use of dopamine agonists as primary symptomatic therapy, the introduction of levodopa as an adjunct when dopamine agonists can no longer sufficiently provide satisfactory clinical control and the use of the lowest dose of levodopa that will provide satisfactory clinical control. In this way symptomatic control is not compromised on theoretical grounds, but the cumulative levodopa dose is minimized in an effort to reduce the likelihood of free radical formation with their potential adverse consequences on disease progression.