Blockade of glutamatergic transmission as treatment for dyskinesias and motor fluctuations in Parkinson's disease |
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Authors: | L Verhagen Metman P Del Dotto PJ Blanchet P van den Munckhof TN Chase |
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Affiliation: | National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland, USA. |
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Abstract: | 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. |
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