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

doi:10.1016/0304-3940(95)11364-3

Neuroscience Letters

Volume 187, Issue 3, 10 March 1995, Pages 165-168

https://doi.org/10.1016/0304-3940(95)11364-3 Get rights and content

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-imine ([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 μM, 0.85 μM and 47 μM, respectively. In the cortex, 1 mM ketobemidone and 1 mM methadone reduced NMDA responses, but not (RS)-2-amino-3-(3-hydroxy5-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.

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

Abstract

Eur. J. Pharmacol.

Trends Neurosci.

Brain Res.

Pain

Neuropharmacology

Eur. J. Pharmacol. Mol. Pharmacol. Sect.

Pain

Curr. Opin. Neurobiol.

Relationship between the inhibition constant (Ki) and the concentration of inhibitor, which causes 50 per cent inhibition (I50) of an enzymatic reaction

Biochem. Pharmacol.