Dextromethorphan improves levodopa-induced dyskinesias in Parkinson's disease

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Abstract
This study assessed the effects of the N-methyl-D-aspartate (NMDA) antagonist dextromethorphan (DM) on levodopa-induced dyskinesias in Parkinson's disease (PD). 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. 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. 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. These findings support the view that drugs acting to inhibit glutamatergic transmission at the NMDA receptors can ameliorate levodopa-associated dyskinesias.