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 (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.
Authors	Melanie A Paquette, Elizabeth G Brudney, Daniel B Putterman, Charles K Meshul, Steven W Johnson, Stephen Paul Berger
Journal	Neuroreport (Neuroreport) Vol. 19 Issue 1 Pg. 111-5 (Jan 08 2008) ISSN: 0959-4965 [Print] England
PMID	18281903 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References	Adrenergic Agents Anti-Anxiety Agents Dopamine Agents Excitatory Amino Acid Antagonists Ligands Pyrimidines alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol Levodopa N-Methylaspartate Dextromethorphan Oxidopamine Amphetamine
Topics	Adrenergic Agents (toxicity) Amphetamine Animals Anti-Anxiety Agents (therapeutic use) Behavior, Animal (drug effects) Dextromethorphan Disease Models, Animal Dopamine Agents (adverse effects) Dyskinesia, Drug-Induced (drug therapy, etiology) Excitatory Amino Acid Antagonists Levodopa (adverse effects) Ligands Male N-Methylaspartate (therapeutic use) Neurotoxicity Syndromes (drug therapy, etiology) Oxidopamine (toxicity) Pyrimidines (therapeutic use) Rats Rats, Sprague-Dawley Time Factors

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!