Role of dopamine agonists in Parkinson’s disease: an update

Abstract

At present, dopamine agonists play an important role in antiparkinsonian therapy since they were proved effective in the management of both advanced- and early-stage Parkinson’s disease. In the latter, they are often regarded as first-choice medication to delay the introduction of levodopa therapy. Despite sharing the capacity to directly stimulate dopamine receptors, dopamine agonists show different pharmacological properties as they act on different subsets of dopamine receptors. This, in theory, provides the advantage of obtaining a different antiparkinsonian activity or safety profile with each agent. However, there is very little evidence that any of the marketed dopamine agonists should be consistently preferred in the management of patients with Parkinson’s disease. Pergolide and cabergoline are now considered a second-line choice after the proven association with valvular fibrosis. Transdermal administration (rotigotine) and subcutaneous infusion (apomorphine) of dopamine receptor agonists are now available alternatives to oral administration and provide continuous dopaminergic stimulation. Continuous subcutaneous apomorphine infusion during waking hours leads to a large reduction in daily ‘off’ time, dyskinesias and levodopa daily dose. Almost all currently used dopamine agonists are able to provide neuroprotective effects towards dopaminergic neurons during in vitro and in vivo experiments. This neuroprotection may be the result of different mechanisms including antioxidation, scavenging of free radicals, suppression of lipid peroxidation and inhibition of apoptosis. However, the disease-modifying effect of these agents in Parkinson’s disease remains to be ascertained.

Keywords::

• apomorphine
• cabergoline
• dopamine agonists
• Parkinson’s disease
• pergolide
• pramipexole
• ropinirole
• rotigotine

Financial & competing interests disclosure

Ubaldo Bonuccelli has acted as a scientific advisor for, or obtained speaker honoraria from Novartis, Boehringer Ingelheim, Pfizer, Chiesi, Schwarz and GlaxoSmithKline. During the past 2 years Ubaldo Bonuccelli has received departmental grants and performed clinical studies for Teva, Novartis, Eisai, GlaxoSK and Boehringer I.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

The authors wish to thank YF Tai for his help during the preparation of the manuscript.