Sigma ligands, but not N-methyl-D-aspartate antagonists, reduce levodopa-induced dyskinesias

Melanie A. Paquette, Elizabeth G. Brudney, Daniel B. Putterman, Charles K. Meshul, Steven W. Johnson, Stephen Paul Berger

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Levodopa (L-DOPA) is the 'gold standard' to treat Parkinson's disease. Unfortunately, dyskinesias detract from its efficacy. Current dyskinesia treatments, including amantadine and dextromethorphan, are thought to work via N-methyl-D-aspartate (NMDA) antagonism, but this hypothesis has not been tested. The NMDA antagonists MK-801 and HA-966 failed to suppress expression of dyskinesias in the 6-hydroxydopamine rat. Dyskinesias, however, were suppressed by the NMDA and sigma (σ)-1 receptor ligand dextromethorphan and by the σ-1 antagonist BMY-14802. Antidyskinetic effects of dextromethorphan may be mediated via mechanisms other than NMDA, including the σ-1 receptor and other binding sites common to dextromethorphan and BMY-14802.

Original languageEnglish (US)
Pages (from-to)111-115
Number of pages5
JournalNeuroReport
Volume19
Issue number1
DOIs
StatePublished - Jan 2008

Keywords

  • 6-hydroxydopamine
  • Levodopa-induced dyskinesias
  • N-methyl-D-aspartate
  • Parkinson's disease
  • Rat
  • Sigma

ASJC Scopus subject areas

  • Neuroscience(all)

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    Paquette, M. A., Brudney, E. G., Putterman, D. B., Meshul, C. K., Johnson, S. W., & Berger, S. P. (2008). Sigma ligands, but not N-methyl-D-aspartate antagonists, reduce levodopa-induced dyskinesias. NeuroReport, 19(1), 111-115. https://doi.org/10.1097/WNR.0b013e3282f3b0d1