NMDA receptor antagonists methadone

When these measures fail, and an opioid appears necessary, methadone, dextroprox5qjhene, tramadol and oxycodone are preferred all possess NMDA-receptor antagonist activity as well as being opioid X-receptor agonists. 

Uncontrolled post-operative acute pain, particularly in patients with a history of chronic pain and opioid dependency, can be quickly and effectively relieved by careful and slow titration of intravenous methadone. Similar results maybe achieved in some opioid-naive patients who are refractory to high doses of potent opioids administered in the post-anesthesia care unit (PACU). This author uses 2.5 mg of methadone every 5-10 minutes to extinguish the fire associated with poorly controlled pain, and, once adequate analgesia is obtained, initiates hydromorphone intravenous PCA bolus with or without continuous infusion. It is likely that the intrinsic NMDA antagonistic property of the d-isomer of methadone blunts NMDA receptor activation and spinal sensitization induced by opioids (opioid hyperalgesia) as well as poorly controlled pain. 

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