Continuous dopaminergic stimulation: clinical aspects and experimental bases

In patients with Parkinson disease, pulsatile administration of dopaminergic drugs is associated with motor fluctuations and dyskinesias. By contrast, treatments that provide more continuous dopaminergic stimulation are associated with less intense motor complications. This can be achieved by using drugs with longer half-lives, delayed release formulations, and routes of administration that permit continuous delivery. The mechanisms by which different modes of dopaminergic treatment (pulsatile or continuous) determine the motor response are not fully understood. However, the use of experimental models of parkinsonism has helped understand the motor complications associated with pulsatile dopamine replacement. These studies have provided important insights into the biochemical and molecular changes in the basal ganglia in response to continuous stimulation. In addition, these models have facilitated the development of new treatments that may stabilize the motor response and the biochemical alterations in the basal ganglia to provide more efficient forms of continuous dopaminergic stimulation in patients with Parkinson disease.