Application of the concept of continuous dopaminergic stimulation for the management of Parkinson's disease.

Continuous dopaminergic stimulation (CDS) is a prominent therapeutic concept for the treatment of Parkinson's disease (PD), which proposes that continuous brain dopamine-receptor stimulation, rather than intermittent doses of oral L-dopa, prevents or manages L-dopa-induced dyskinesias (LIDs). In the normal situation, dopaminergic neurons in the substantia nigra pars compacta fire tonically to keep the dopamine receptor stimulation at a steady-state level. But when the dopaminergic pathway is impaired, the dopamine receptor stimulation becomes intermittent or pulsatile. This pulsatile stimulation causes a series of gene and protein changes in striatal neurons, leading to alterations in the fi ring patterns of basal ganglia neurons that result in LIDs. Studies in animal models and clinical trials of PD have shown that approaches providing CDS, currently including patches, extended-release formulations of L-dopa or dopamine agonists, continuous delivery of apomorphine and duodenal L-dopa infusion, are associated with a decreased risk of LIDs. In this review, we summarize both preclinical and clinical evidence for the five methods that may provide CDS in theory and compare the advantages and disadvantages of these methods.