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

doi:10.1097/WNR.0b013e3282f3b0d1

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 journal › Article › peer-review

19 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 language	English (US)
Pages (from-to)	111-115
Number of pages	5
Journal	NeuroReport
Volume	19
Issue number	1
DOIs	https://doi.org/10.1097/WNR.0b013e3282f3b0d1
State	Published - Jan 2008
Externally published	Yes

Keywords

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

ASJC Scopus subject areas

General Neuroscience

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10.1097/WNR.0b013e3282f3b0d1

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

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.",

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author = "Paquette, {Melanie A.} and Brudney, {Elizabeth G.} and Putterman, {Daniel B.} and Meshul, {Charles K.} and Johnson, {Steven W.} and Berger, {Stephen Paul}",

year = "2008",

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doi = "10.1097/WNR.0b013e3282f3b0d1",

language = "English (US)",

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T1 - Sigma ligands, but not N-methyl-D-aspartate antagonists, reduce levodopa-induced dyskinesias

AU - Paquette, Melanie A.

AU - Brudney, Elizabeth G.

AU - Putterman, Daniel B.

AU - Meshul, Charles K.

AU - Johnson, Steven W.

AU - Berger, Stephen Paul

PY - 2008/1

Y1 - 2008/1

N2 - 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.

AB - 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.

KW - 6-hydroxydopamine

KW - Levodopa-induced dyskinesias

KW - N-methyl-D-aspartate

KW - Parkinson's disease

KW - Rat

KW - Sigma

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

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