Blockade of glutamatergic transmission as treatment for dyskinesias and motor fluctuations in Parkinson's disease

Amino Acids. 1998;14(1-3):75-82. doi: 10.1007/BF01345246.

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.

MeSH terms

  • Amantadine / pharmacology
  • Amantadine / therapeutic use
  • Clinical Trials as Topic
  • Controlled Clinical Trials as Topic
  • Dextromethorphan / pharmacology
  • Dextromethorphan / therapeutic use
  • Dextrorphan / pharmacology
  • Dextrorphan / therapeutic use
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Amino Acid Antagonists / therapeutic use*
  • Glutamic Acid / metabolism*
  • Humans
  • Levodopa / pharmacology
  • Levodopa / therapeutic use
  • Movement Disorders / drug therapy*
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / metabolism
  • Parkinson Disease / physiopathology
  • Psychomotor Performance / drug effects*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors

Substances

  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Dextrorphan
  • Glutamic Acid
  • Levodopa
  • Dextromethorphan
  • Amantadine