AMANTADINE AS TREATMENT FOR DYSKINESIAS AND MOTOR FLUCTUATIONS IN PARKINSONS-DISEASE

Objective: To determine the effects of the N-methyl-D-aspartate (NMDA) antagonist amantadine on levodopa-associated dyskinesias and motor fl uctuations in Parkinson's disease (PD). Background: NMDA receptor bloc kade can ameliorate levodopa-induced dyskinesias in primates and PD pa tients. Amantadine, a well-tolerated and modestly effective antiparkin sonian agent, was recently found to possess NMDA antagonistic properti es. Methods: Eighteen patients with advanced PD participated in a doub le-blind, placebo-controlled, cross-over study. At the end of each 3-w eek treatment arm, parkinsonian and dyskinesia scores were obtained du ring a steady-state intravenous levodopa infusion. Motor fluctuations and dyskinesias were also documented with patient-kept diaries and Uni fied Parkinson's Disease Rating Scale (UPDRS) interviews. Results: In the 14 patients completing this trial, amantadine reduced dyskinesia s everity by 60% (p = 0.001) compared to placebo, without altering the a ntiparkinsonian effect of levodopa. Motor fluctuations occurring with patients' regular oral levodopa regimen also improved according to UPD RS and patient-kept diaries. Conclusions: These findings suggest that amantadine given as adjuvant to levodopa can markedly improve motor re sponse complications and support the view that hyperfunction of NMDA r eceptors contributes to the pathogenesis of levodopa-associated motor complications.