Clinical strategies to prevent and delay motor complications

Current evidence suggests that motor complications associated with long-term L-dopa treatment in patients with Parkinson's disease (PD) are the consequence of two factors: the disease course, with progressive destruction of dopaminergic terminals, and the pulsatile nonphysiologic stimulation of dopamine receptors caused by multiple administrations of L-dopa. Pharmacokinetic considerations suggest that continuous dopaminergic stimulation (CDS) may be achieved either by using long-acting dopamine agonists (DAs) or by continuously delivering L-dopa. A variety of therapeutic strategies based on CDS have been proposed to reduce motor complications that occur after long-term L-dopa treatment. Several recent studies have suggested the possibility of preventing motor complications by initiating treatment with DAs, including pramipexole, cabergoline, and ropinirole. Such a preventive effect may be due to the CDS provided by the agonists. In addition, new experimental evidence suggests that initial treatment with pramipexole compared with L-dopa not only reduces the 4-year risk of developing motor complications but also is associated with less loss of dopaminergic terminals, as assessed by SPECT. These data highlight the critical role of DAs in the treatment of PD. Compared with L-dopa, these drugs provide a more physiologic stimulation of dopaminergic receptors and, in the case of pramipexole and ropinirole, may contribute to sparing of dopaminergic terminals, thus affecting both factors responsible for the development of motor complications.