Role of dopamine receptor agonists in the treatment of early Parkinson's disease

Abstract

In the last two decades, the usefulness of dopamine receptor agonists in the symptomatic treatment of Parkinson' disease (PD) has been demonstrated in many randomized controlled clinical trials. The initial role of such compounds as an adjunctive therapy to l-dopa to improve motor fluctuations has now expanded to the treatment of early PD as initial monotherapy. The rationale for the use of dopamine receptor agonists in early disease is to delay or reduce the incidence of motor complications resulting from long-term l-dopa therapy, probably by virtue of less pulsatile stimulation of postsynaptic dopamine receptors. Indeed, controlled trials with both ergot and non-ergot dopamine receptor agonists, such as cabergoline, pergolide, pramipexole and ropinirole, have shown lower risk of motor fluctuations and dyskinesias than with l-dopa, when used as monotherapy in early PD patients. The benefit of agonists in preventing motor complications is, however, balanced by a smaller effect on motor symptoms compared with l-dopa. Moreover, a greater incidence of side-effects, particularly somnolence, hallucinations and leg oedema, occurs with dopamine receptor agonists. Because of the risk of fibrotic reactions, ergot derivatives (bromocriptine, cabergoline, and pergolide) are not recommended as first-line antiparkinsonian medication. In younger patients, who are usually more prone to developing l-dopa-induced motor complications, the initial treatment with dopamine receptor agonists can be recommended. Further pharmacological refinement of PD management with these drugs may result from new formulations of old drugs, such as once-daily prolonged-release ropinirole, or new agonists, such as the rotigotine patch, that can allow more continuous dopaminergic stimulation and improve patient compliance with the drug treatment. Theoretically, another advantage of dopamine receptor agonists is the potential for a neuroprotective effect, through many different mechanisms of actions. Preliminary controlled trials with pramipexole and ropinirole, although encouraging, did not provide conclusive proof of the disease-modifying effect of dopamine receptor agonists; large controlled clinical trials are now underway and results are expected soon.