Dextromethorphan improves levodopa-induced dyskinesias in Parkinson's disease.
OBJECTIVE
This study assessed the effects of the N-methyl-D-aspartate (NMDA) antagonist dextromethorphan (DM) on levodopa-induced dyskinesias in Parkinson's disease (PD).


BACKGROUND
Recent experimental evidence suggests that increased synaptic efficacy of NMDA receptors expressed on basal ganglia neurons may play a role in the pathophysiology of levodopa-induced motor response complications.


METHODS
DM was given to six PD patients with motor fluctuations in a double-blind, placebo-controlled, cross-over study. At the end of each 3-week study arm, patients received several brief i.v. levodopa infusions while parkinsonian symptoms and dyskinesias were frequently scored. Levodopa dose-response curves for antiparkinsonian and dyskinetic effects were then compared for each study arm.


RESULTS
With DM, average and maximum dyskinesia scores improved by >50%, without compromising the antiparkinsonian response magnitude or duration of levodopa, although in some subjects the levodopa threshold dose was slightly higher with DM than with placebo.


CONCLUSIONS
These findings support the view that drugs acting to inhibit glutamatergic transmission at the NMDA receptors can ameliorate levodopa-associated dyskinesias.
Experimental Therapeutics Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892-1406, USA.
L
L
Verhagen Metman
P
P
Del Dotto
R
R
Natté
P
P
van den Munckhof
T N
TN
Chase
D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects*; D000996:Antitussive Agents / Q000008:administration & dosage*; D003915:Dextromethorphan / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D000978:Antiparkinson Agents; D000996:Antitussive Agents; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007980:Levodopa; D003915:Dextromethorphan