Dopamine agonists and neuroprotection in Parkinson's disease

There is increasing interest in the potential of dopamine agonists to provide a neuroprotective effect and to alter the natural course of levodopa-treated Parkinson's disease (PD). Theoretically, such a protective effect might derive from (a) a levodopa sparing effect, (b) stimulation dopamine autoreceptors resulting in decreased dopamine synthesis, release, and turnover, (c) direct anti-oxidant effects, and (d) restoration of dopaminergic tone to the dopamine-denervated brain so as to restore inhibition to the subthalamic nucleus and thereby diminish STN-mediated excitotoxicity. Preclinical studies have demonstrated that dopamine agonists reduce dopamine formation in comparison to levodopa, protect cultured dopaminergic neurons from a variety of toxins including levodopa, and protect dopaminergic neurons from toxins and age-related degeneration in some rodent models of parkinsonism. Based on these findings, several clinical trials have been initiated in patients with early PD to test the effect of dopamine agonists on clinical and neuroimaging markers of disease progression.