Are dopamine receptor agonists neuroprotective in Parkinson's disease?

Dopamine receptor agonists are playing an increasingly important role in th e treatment of not only patients with advanced Parkinson's disease and thos e with levodopa-induced motor fluctuations, but also in the early treatment of the disease. This shift has been largely due to the demonstrated levodo pa-sparing effect of dopamine agonists and their putative neuroprotective e ffect, with evidence for the latter being based largely on experimental in vitro and in vivo studies. In this article we review the evidence for neuro protection by the dopamine agonists pramipexole, ropinirole, pergolide, bro mocriptine and apomorphine in cell cultures and animal models of injury to the substantia nigra. Most of the studies suggest that dopamine agonists may have neuroprotective effects via direct scavenging of free radicals or increasing the activitie s of radical-scavenging enzymes, and enhancing neurotrophic activity. Howev er, the finding that pramipexole can normalise mitochondrial membrane poten tial and inhibit activity of caspase-3 in cytoplasmic hybrid cells derived from mitochondrial DNA of patients with nonfamilial. Alzheimer's disease su ggests an even broader implication for the neuroprotective role of dopamine agonists. Although the clinical evidence for neuroprotection by dopamine a gonists is still limited, the preliminary results from several ongoing clin ical trials are promising. Several longitudinal studies are currently in pr ogress designed to demonstrate a delay or slowing of progression of Parkins on's disease using various surrogate markers of neuronal degeneration such as F-18-levodopa positron emission tomography and I-123 beta -CIT (carbomet hoxy-beta -4-iodophenyl-nortropane) single positron emission computed tomog raphy. The results of these experimental and clinical studies will improve our understanding of the action of dopamine agonists and provide critical i nformation needed for planning future therapeutic strategies for Parkinson' s disease and related neurodegenerative disorders.