Effects of a NR2B selective NMDA glutamate antagonist, CP-101,606, on dyskinesia and Parkinsonism.

Abstract

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 approximately 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.

• Authors: John G Nutt, Steven A Gunzler, Trish Kirchhoff, Penelope Hogarth, Jerry L Weaver, Michael Krams, Brenda Jamerson, Frank S Menniti, Jaren W Landen
• Journal: Movement disorders : official journal of the Movement Disorder Society (Mov Disord) Vol. 23 Issue 13 Pg. 1860-6 (Oct 15 2008) ISSN: 1531-8257 [Electronic] United States
• PMID: 18759356 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2008 Movement Disorder Society.

Chemical References

• Dopamine Agents
• Excitatory Amino Acid Antagonists
• Piperidines
• Levodopa
• traxoprodil mesylate

Topics

• Aged
• Cross-Over Studies
• Dopamine Agents (adverse effects)
• Double-Blind Method
• Dyskinesias (drug therapy, etiology)
• Excitatory Amino Acid Antagonists (therapeutic use)
• Humans
• Levodopa (adverse effects)
• Middle Aged
• Parkinsonian Disorders (complications, drug therapy)
• Piperidines (therapeutic use)
• Severity of Illness Index