Continuous dopamine-receptor stimulation in advanced Parkinson's disease

Intermittent or pulsatile dopamine-receptor stimulation is postulated to in duce plastic changes in motor systems that are responsible for the developm ent of the motor fluctuations and dyskinesia that complicate long-term L-do pa therapy of Parkinson's disease. As a corollary to this hypothesis, conti nuous dopamine-receptor stimulation can avoid or reverse these complication s. Such continuous stimulation is unlikely to mimic completely the normal f unction of the dopaminergic system, but should avoid the supra-physiologica l swings in extracellular dopamine that accompany intermittent L-dopa dosin g. The concern is that this continuous stimulation might induce tolerance r ather than sensitization to some effects of L-dopa. Open clinical trials su pport the value of continuous dopaminergic stimulation in Parkinson's disea se with established motor complications, but rigorous studies, although exp erimentally difficult, are needed.