Blockade of glutamatergic transmission as treatment for dyskinesias and motor fluctuations in Parkinson's disease.
In animal models of Parkinson's disease (PD), glutamate antagonists diminish levodopa (LD)-associated motor fluctuations and dyskinesias. We sought to investigate if these preclinical observations can be extended to the human disease, by evaluating the effects of three non-competitive NMDA antagonists (dextrorphan, dextromethorphan and amantadine) on the motor response to LD in patients with advanced PD. In four separate trials, adjuvant therapy with these drugs reduced LD-induced dyskinesias and motor fluctuations. These findings support the view that drugs acting to inhibit glutamatergic transmission at the NMDA receptor can ameliorate LD associated motor response complications.
Verhagen Metman
L
L
National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Del Dotto
P
P
Blanchet
P J
PJ
van den Munckhof
P
P
Chase
T N
TN
D000547:Amantadine / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D018849:Controlled Clinical Trials as Topic; D003915:Dextromethorphan / Q000494:pharmacology / Q000627:therapeutic use; D003917:Dextrorphan / Q000494:pharmacology / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007980:Levodopa / Q000494:pharmacology / Q000627:therapeutic use; D009069:Movement Disorders / Q000188:drug therapy*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D011597:Psychomotor Performance / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D003917:Dextrorphan; D018698:Glutamic Acid; D007980:Levodopa; D003915:Dextromethorphan; D000547:Amantadine