The use of NMDA-receptor antagonists in the treatment of chronic pain

Clin J Pain. 2000 Jun;16(2 Suppl):S73-9. doi: 10.1097/00002508-200006001-00013.


Chronic pain can be maintained by a state of sensitization within the central nervous system that is mediated in part by the excitatory amino acids glutamate and aspartate binding to the N-methyl-D-aspartate (NMDA) receptor. A number of antagonists to the NMDA receptor are antinociceptive in animal models but are associated with significant dose-limiting side effects. Commercially available NMDA-receptor antagonists include ketamine, dextromethorphan, memantine, and amantadine. The opioids methadone, dextropropoxyphene, and ketobemidone are also antagonists at the NMDA receptor. The NMDA-receptor antagonists have a significant impact on the development of tolerance to opioid analgesics. Consequently, NMDA-receptor antagonists may represent a new class of analgesics and may have potential as coanalgesics when used in combination with opioids.

Publication types

  • Review

MeSH terms

  • Chronic Disease
  • Excitatory Amino Acid Antagonists / therapeutic use*
  • Humans
  • Pain / drug therapy*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*


  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate