Ketobemidone, methadone and pethidine are non-competitive N-methyl-D-aspartate (NMDA) antagonists in the rat cortex and spinal cord.

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Ebert B, Andersen S, Krogsgaard-Larsen P

Ketobemidone, methadone and pethidine are non-competitive N-methyl-D-aspartate (NMDA) antagonists in the rat cortex and spinal cord.

Neurosci Lett. 1995 Mar 10;187(3):165-8.

PubMed ID

7624018 [ View in PubMed

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Abstract

The opiate agonists, ketobemidone, methadone and pethidine, were evaluated as N-methyl-D-aspartate (NMDA) receptor antagonists using the rat cortical wedge preparation and the neonatal rat spinal cord preparation for electrophysiological studies and [3H](RS)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-im ine ([3H]MK-801) binding experiments using rat forebrain homogenates. Ketobemidone, methadone and pethidine were inhibitors of [3H]MK-801 binding with Ki values of 26 microM, 0.85 microM and 47 microM, respectively. In the cortex, 1 mM ketobemidone and 1 mM methadone reduced NMDA responses, but not (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionic acid (AMPA) or kainate responses in an use-dependent manner, whereas 1 mM pethidine was devoid of antagonist activity. In the spinal cord preparation, the activities of ketobemidone and methadone were weaker than in cortex. In contrast, pethidine was equipotent with ketobemidone in the spinal cord. These results suggest that ketobemidone and methadone may be useful therapeutic agents in conditions where a combined opiate agonist and NMDA antagonist treatment is desired.

DrugBank Data that Cites this Article

Drug Targets

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