Do dopamine agonists provide neuroprotection?

Abstract

Many reports provide evidence that certain dopamine (DA) agonists, such as pramipexole or the ergot-derived drugs bromocriptine and pergolide, exhibit neuroprotective effects in in vivo and in vitro experiments, whereas other DA agonists are not known to have such effects. The neuroprotective hypothesis for the action of DA agonists is a very attractive working hypothesis, and some of its tenets are derived from the oxidative stress hypothesis for neurodegeneration. If this neuroprotective hypothesis about DA agonists is correct, DA agonist therapy for Parkinson's disease (PD) will become increasingly important. Whereas most neurologists appear to believe that DA agonists have neuroprotective effects, the oxidative stress (free radical) hypothesis, although fascinating, is still controversial. This article reviews experimental studies on the neuroprotective effects of DA agonists from the clinical standpoint and critically examines the justifications for their clinical use as neuroprotective agents. Studies concerning DA agonist monotherapy, especially de novo treatment studies, provide the most relevant information. Several reports have known that DA agonists delayed the start of levodopa but also have revealed that it was impossible to continue administration of DA agonists alone for long-term treatment of PD. In conclusion, at present there is no clinical evidence that DA agonists have direct neuroprotective effects against PD.