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

John G. Nutt, Steven A. Gunzler, Trish Kirchhoff, Penelope Hogarth, Jerry L. Weaver, Michael Krams, Brenda Jamerson, Frank S. Menniti, Jaren W. Landen

Research output: Contribution to journalArticle

96 Scopus citations

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 ∼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.

Original languageEnglish (US)
Pages (from-to)1860-1866
Number of pages7
JournalMovement Disorders
Volume23
Issue number13
DOIs
StatePublished - Oct 15 2008

Keywords

  • Amnesia
  • CP-101,606
  • Dissociation
  • Dyskinesia
  • Levodopa
  • NR2B subunit selective glutamate antagonist
  • Parkinson's disease

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Nutt, J. G., Gunzler, S. A., Kirchhoff, T., Hogarth, P., Weaver, J. L., Krams, M., Jamerson, B., Menniti, F. S., & Landen, J. W. (2008). Effects of a NR2B selective NMDA glutamate antagonist, CP-101,606, on dyskinesia and parkinsonism. Movement Disorders, 23(13), 1860-1866. https://doi.org/10.1002/mds.22169