Journal
MOVEMENT DISORDERS
Volume 23, Issue 13, Pages 1860-1866Publisher
WILEY
DOI: 10.1002/mds.22169
Keywords
Parkinson's disease; levodopa; dysminesia; NR2B subunit selective glutamate antagonist; CP-101.606; amnesia; dissociation
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Funding
- Pfizer Global Research and Development
- Oregon Clinical and Translational Research Institute [UL1-RR024140]
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Glutamate antagonists decrease dyskinesia and augment the antiparkinsonian effects of levodopa in animal models of Parkinson's disease (PD). In a randomized, double-blind, placebo-controlled clinical trial, we investigated the acute effects of placebo and two doses of a NR2B subunit selective NMDA glutamate antagonist, CP-101.606 on the response to 2-hour levodopa infusions in 12 PD subjects with motor fluctuations and dyskinesia. Both doses of CP-101.606 reduced the maximum severity of levodopa-induced dyskinesia similar to 30% but neither dose improved Parkinsonism. CP-101.606 was associated with a dose-related dissociation and amnesia. These results support the hypothesis that glutamate antagonists may be useful antidyskinetic agents. However, future studies will have to determine if the benefits of dyskinesia suppression can be achieved without adverse cognitive effects. (C) 2008 Movement Disorder Society.
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