ABSTRACT
Even though oral levodopa (combined with a peripheral dopa decarboxylase inhibitor) remains the most efcacious symptomatic drug treatment for Parkinson’s disease (PD), it is not devoid of problems. The emergence of motor response complications in levodopa-treated PD patients has puzzled and fascinated neurologists for 40 years. Sooner or later, most patients experience a predictable (so-called wearing-off effect) and less often unpredictable return in parkinsonian disability during the day, associated with nonmotor symptoms (neuropsychiatric, cognitive, or dysautonomic) and various dyskinesias, for reasons that remain elusive. Given the fact that the very short plasma half-life, poor bioavailability, and erratic absorption of oral levodopa are factors consistently present throughout the illness, and the lack of demonstration of unequivocal changes in peripheral pharmacokinetic handling of levodopa over time, attention shifted toward acquired changes in central pharmacokinetic properties and additional pharmacodynamic factors to explain and eventually correct the Ÿuctuations in levodopa motor response. Experimental attempts have tried to match the fairly good correlation between stable plasma levels of levodopa and sustained motor response with ways to continuously supply the dopamine precursor by bypassing the oral route.
