Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson's disease

Objective: To determine the effects of the N-methyl-D-aspartate (NMDA) anta gonist amantadine on levodopa-associated dyskinesias and motor fluctuations in Parkinson's disease (PD). Background: NMDA receptor blockade can amelio rate levodopa-induced dyskinesias in primates and PD patients. Amantadine, a well-tolerated and modestly effective antiparkinsonian agent, was recentl y found to possess NMDA antagonistic properties. Methods: Eighteen patients with advanced PD participated in a double-blind, placebo-controlled, cross -over study. At the end of each 3-week treatment arm, parkinsonian and dysk inesia scores were obtained during a steady-state intravenous levodopa infu sion. Motor fluctuations and dyskinesias were also documented with patient- kept diaries and Unified Parkinson's Disease Rating Scale (UPDRS) interview s. Results. In the 14 patients completing this trial, amantadine reduced dy skinesia averity by 60% (p = 0.001) compared to placebo, without altering t he antiparkinsonian effect of levodopa. Motor everity by 60% (p = 0.001) co mpared to placebo, without altering the antiparkinsonian effect of levodopa . Motor fluctuations occurring with patients' regular oral levodopa regimen also improved according to UPDRS and patient-kept diaries. Conclusions: Th ese findings suggest that amantadine given as adjuvant to levodopa can mark edly improve motor response complications and support the view that hyperfu nction of NMDA receptors contributes to the pathogenesis of levodopa-associ ated motor complications.