Response to l -dopa in PD

Motor fluctuations in a patient with advanced PD are among the most dramatic clinical phenomena encountered by neurologists. The rapid and frequent oscillations between immobility and mobility emphasize the 1- to 2-hour plasma half-life of l-dopa and the correspondingly short duration of action of each dose of drug. This clinical observation has dominated our thinking about l-dopa and guided our attempts to improve treatment for PD. It is less appreciated that l-dopa has therapeutic effects that persist much longer than its plasma half-life. Cotzias et al., in their seminal publication on the therapeutic efficacy of oral dopa, noted that “ . . . the re-establishment of the base-line state with abrupt termination of the drug [D,L-dopa], after prolonged therapy, was much longer (four to fourteen days).”1 Muenter and Tyce named the l-dopa–induced motor improvement that had a gradual onset with repeated dosing and declined over days upon drug withdrawal the …