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Abstract

Objective: To determine the effects of the N-methyl-D-aspartate (NMDA) antagonist amantadine on levodopa-associated dyskinesias and motor fluctuations in Parkinson's disease (PD).
Background: NMDA receptor blockade can ameliorate levodopa-induced dyskinesias in primates and PD patients. Amantadine, a well-tolerated and modestly effective antiparkinsonian agent, was recently 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 dyskinesia scores were obtained during a steady-state intravenous levodopa infusion. Motor fluctuations and dyskinesias were also documented with patient-kept diaries and Unified Parkinson's Disease Rating Scale (UPDRS) interviews.
Results: In the 14 patients completing this trial, amantadine reduced dyskinesia severity by 60% (p = 0.001) compared 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: These findings suggest that amantadine given as adjuvant to levodopa can markedly improve motor response complications and support the view that hyperfunction of NMDA receptors contributes to the pathogenesis of levodopa-associated motor complications.

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Published In

Neurology®
Volume 50Number 5May 1998
Pages: 1323-1326
PubMed: 9595981

Publication History

Published online: May 1, 1998
Published in print: May 1998

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Authors

Affiliations & Disclosures

L. Verhagen Metman, MD
From the Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
P. Del Dotto, MD
From the Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
P. van den Munckhof, BS
From the Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
J. Fang, MD
From the Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
M. M. Mouradian, MD
From the Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
T. N. Chase, MD
From the Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.

Notes

Address correspondence and reprint requests to Dr. Thomas N. Chase, National Institutes of Health, Building 10, Room 5C104, 10 CENTER DR MSC 1406, Bethesda, MD 20892-1406.

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