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

AUDITORY AND VESTIBULAR SYSTEMS
Neuroreport. 19(1):111-115, January 8, 2008.
Paquette, Melanie A. a c; Brudney, Elizabeth G. c; Putterman, Daniel B. b c; Meshul, Charles K. a c; Johnson, Steven W. b c; Berger, Stephen Paul a c

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 ([sigma])-1 receptor ligand dextromethorphan and by the [sigma]-1 antagonist BMY-14802. Antidyskinetic effects of dextromethorphan may be mediated via mechanisms other than NMDA, including the [sigma]-1 receptor and other binding sites common to dextromethorphan and BMY-14802.