Role of COMT inhibitors and dopamine agonists in the treatment of motor fluctuations.

Although levodopa remains the most effective drug for the symptomatic treatment of Parkinson's disease (PD), there are significant limitations to its chronic use. Growing preclinical and clinical evidence suggests that the severity of motor fluctuations is influenced both by PD severity and pulsatile stimulation of striatal dopamine receptors. Current management of motor fluctuations is based primarily on strategies to prolong the effects of dopaminergic stimulation. This prolongation is accomplished either through the use of long-acting dopaminergic drugs or prolonging of the effects of levodopa. During the past decade, the armamentarium of dopamine agonists increased and agents that prolong the plasma half-life of levodopa became available. Furthermore, recent clinical trials provide evidence-based approaches to improve the management of motor fluctuations in patients with advanced and early PD. (c) 2005 Movement Disorder Society.