Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson's disease.
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.
Verhagen Metman
L
L
Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1406, USA.
Del Dotto
P
P
van den Munckhof
P
P
Fang
J
J
Mouradian
M M
MM
Chase
T N
TN
D000328:Adult; D000368:Aged; D000547:Amantadine / Q000627:therapeutic use*; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy*; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000009:adverse effects; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
D000978:Antiparkinson Agents; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007980:Levodopa; D000547:Amantadine