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

Mov Disord. 2008 Oct 15;23(13):1860-6. doi: 10.1002/mds.22169.

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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