Clinical pharmacology of levodopa-induced dyskinesia

Levodopa-induced dyskinesia (LID) is a major impediment to the successful t herapy of Parkinson's disease. The development of LID is facilitated by dop aminergic denervation but may not require denervation. Repeated levodopa do sing is necessary to induce dyskinesia, implying the development of sensiti zation to levodopa. There is inconclusive evidence on whether repeated dosi ng lowers the threshold (shifts the levodopa-dyskinesia response curve to t he left), increases the severity of dyskinesia (increases the maximum effec t that is initially zero) or induces more complex changes in the dose-respo nse curve. Once a patient develops LID, the severity of LID is not dose res ponsive, but the duration of dyskinesia is. Clinically, it is very difficul t to separate the antiparkinsonian and dyskinetic effects of levodopa. Whet her this separation is possible with more selective agonists with antiparki nsonian effects that are equipotent to levodopa is unknown. The fact that s elective stimulation of the pallidum does not separate antiparkinsonian and dyskinetic actions implies that they are closely related anatomically and physiologically.