Current status of dopamine agonists in Parkinson's disease management.

The occurrence of late side effects of long term levodopa therapy (fluctuations in motor performance, abnormal movements, and symptoms unresponsive to dihydroxyphenylalanine) led to the search for novel anti-Parkinsonian drugs. Dopamine agonists are one of the newer families of anti-Parkinsonian agents, and they include ergot derivatives and apomorphine, which can be used in the different stages of Parkinson's disease. Ergot derivatives (bromocriptine, lisuride, pergolide) are believed to act independently of the dying cells of the substantia nigra, acting instead directly on postsynaptic dopamine receptors in the striatum. They are usually used in combination with levodopa when late side effects occur, especially 'wearing-off' or decreased efficacy of levodopa. They can also be prescribed earlier in combination with levodopa in de novo Parkinsonian patients, and in this setting are thought to delay the occurrence of late adverse motor effects. In some patients, monotherapy with relatively high doses of ergot derivatives can be used as initial treatment. However, their efficacy often decreases after 1 to 3 years, thus justifying a late combination with levodopa. Apomorphine is a non-ergot derivative dopamine agonist, which is used subcutaneously for the treatment of severe 'off' refractory periods, in combination with other dopaminergic drugs without changing the patient's routine drug regimen.