Dopamine agonists in Parkinson's disease - What is their role in early treatment?

Dopamine receptor agonists are pharmacological agents with diverse physical and chemical properties that share the capacity to stimulate dopamine receptors and provide an antiparkinsonian effect. Currently available dopamine agonists belong to 2 classes: ergot (bromocriptine, lisuride, pergolide, cabergoline) and non-ergot (apomorphine, ropinirole, pramipexole) derivatives, each having a different pharamacological profile and different affinity for the dopaminergic receptors acid subtypes. Dopamine agonists act directly on striatal dopamine receptors. Unlike levodopa, they do not require metabolic conversion to an active form, and so their effects are independent of the degenerative state of dopaminergic terminals. They can selectively stimulate subclasses of dopamine receptors, theoretically reducing the incidence of adverse effects. Dopamine agonists do not compete with circulating plasma amino acids for absorption and transport into the brain and they do not generate free radicals or induce oxidative stress. Recently it has been demonstrated that dopamine D-2 receptor-selective agonists may protect against glutamate-induced neurotoxicity in cultured neurons. Dopamine agonists have been employed since 1974 as adjuncts to levodopa for patients with advanced Parkinson's disease. However, several studies have demonstrated the capacity of these drugs to improve motor fluctuations and reduce dyskinesia in parkinsonian patients whose response to levodopa is associated with motor complications. Moreover dopamine agonists provide a levodopa sparing effect. In the past some authors reported a clear symptomatic effect of dopamine agonists used in monotherapy in patients with rie novo Parkinson's disease but because of the higher incidence of adverse effects compared with levodopa monotherapy this therapeutic strategy was not widely used. Recently the therapeutic approach to Parkinson's disease has begun to change and the role of dopamine agonists become more prominent especially in early treatment (i.e. in patients who have not previously received any other dopaminergic treatment for Parkinson's disease). There are now convincing animal studies which show that dopamine agonists induce less motor complications than levodopa when used as long term treatment. Clinical studies have shown that early treatment with dopamine agonists is associated with a lower incidence of motor fluctuations and dyskinesias. Controlled clinical trials have demonstrated that dopamine agonists may be as effective as levodopa in improving parkinsonian symptoms at least in the initial stages of the disease. Their use as initial therapy is therefore strongly recommended in young patients who have a higher risk of developing levodopa-induced motor complications. In elderly patients, cognitive impairment and cardiovascular disease are important modifiers in determining the appropriate pharmacological intervention. The higher incidence of systemic adverse effects induced by dopamine agonists can be controlled with slow titration of dosage and coadministration of domperidone.