Opioid analgesics as noncompetitive N-methyl-D-aspartate (NMDA) antagonists.

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Ebert B, Thorkildsen C, Andersen S, Christrup LL, Hjeds H

Opioid analgesics as noncompetitive N-methyl-D-aspartate (NMDA) antagonists.

Biochem Pharmacol. 1998 Sep 1;56(5):553-9. doi: 10.1016/s0006-2952(98)00088-4.

PubMed ID

9783723 [ View in PubMed

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Abstract

Much evidence points to the involvement of N-methyl-D-aspartate (NMDA) receptors in the development and maintainance of neuropathic pain. In neuropathic pain, there is generally involved a presumed opioid-insensitive component, which apparently can be blocked by NMDA receptor antagonists. However, in order to obtain complete analgesia, a combination of an NMDA receptor antagonist and an opioid receptor agonist is needed. Recent in vitro data have demonstrated that methadone, ketobemidone, and dextropropoxyphene, in addition to being opioid receptor agonists, also are weak noncompetitive NMDA receptor antagonists. Clinical anecdotes suggest that the NMDA receptor antagonism of these opioids may play a significant role in the pharmacological action of these compounds; however, no clinical studies have been conducted to support this issue. In the present commentary, we discuss evidence for the NMDA receptor antagonism of these compounds and its relevance for clinical pain treatment; an overview of structure-activity relationships for the relevant opioids as noncompetitive NMDA receptor antagonists also is given. It is concluded that although the finding that some opioids are weak noncompetitive NMDA receptor antagonists in vitro has created much attention among clinicians, no clinical studies have been conducted to evaluate the applicability of these compounds in the treatment of neuropathic pain conditions.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Dextropropoxyphene	NMDA receptor (Protein Group)	Protein group	Humans	Unknown	Antagonist	Details
Ketobemidone	NMDA receptor (Protein Group)	Protein group	Humans	Unknown	Antagonist	Details
Methadone	NMDA receptor (Protein Group)	Protein group	Humans	Yes	Antagonist	Details