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Updated: Oct 15, 2026

Intracranial Pharmacotherapy and Pain Assays in Rodents
Published on: April 9, 2019
The use of NMDA-receptor antagonists in the treatment of chronic pain
1Department of Neurology, Emory University Medical Center, Atlanta, Georgia, USA. David_Hewitt@emory.org
Abstract:
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.
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