Sigma ligands, but not N-methyl-D-aspartate antagonists, reduce levodopa-induced dyskinesias.
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.
Paquette
Melanie A
MA
Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, Oregon, USA. paquette@ohsu.edu
Brudney
Elizabeth G
EG
Putterman
Daniel B
DB
Meshul
Charles K
CK
Johnson
Steven W
SW
Berger
Stephen Paul
SP
D018663:Adrenergic Agents / Q000633:toxicity; D000661:Amphetamine; D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D003915:Dextromethorphan; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000009:adverse effects; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000209:etiology; D018691:Excitatory Amino Acid Antagonists; D007980:Levodopa / Q000009:adverse effects; D008024:Ligands; D008297:Male; D016202:N-Methylaspartate / Q000627:therapeutic use*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy / Q000209:etiology; D016627:Oxidopamine / Q000633:toxicity; D011743:Pyrimidines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D018663:Adrenergic Agents; D014151:Anti-Anxiety Agents; D015259:Dopamine Agents; D018691:Excitatory Amino Acid Antagonists; D008024:Ligands; D011743:Pyrimidines; C050408:alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol; D007980:Levodopa; D016202:N-Methylaspartate; D003915:Dextromethorphan; D016627:Oxidopamine; D000661:Amphetamine