Quantitative studies on some antagonists of N-methyl D-aspartate in slices of rat cerebral cortex.

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Harrison NL, Simmonds MA

Quantitative studies on some antagonists of N-methyl D-aspartate in slices of rat cerebral cortex.

Br J Pharmacol. 1985 Feb;84(2):381-91.

PubMed ID

2858237 [ View in PubMed

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Abstract

Coronal sections of rat brain (500 micron thick) were trimmed to form 'wedges' of tissue consisting of cerebral cortex and corpus callosum. When these slices were placed in a two-compartment bath, the cortical tissue could be depolarized, relative to the corpus callosum, by superfusions of high K+, or by amino acids such as L-glutamate, L-aspartate, quisqualate, kainate and N-methyl D-aspartate (NMDA). Responses to NMDA were reduced by magnesium ions, by the organic antagonists (-)-2-amino 5-phosphonovalerate (APV) and 2-amino 7-phosphonoheptanoate (APH), and by the dissociative anaesthetic ketamine. In this preparation, all these antagonists shifted the NMDA dose-response curve to the right in a parallel manner. A Schild plot for Mg2+ had a slope significantly less than unity, indicative of a non-competitive action, whilst Schild plots for (-)-APV, APH and ketamine appeared linear and had slopes of approximately 1. Analysis of the results of combination experiments suggested that the presumed competitive antagonists, (-)-APV and APH, share a common site of action as NMDA antagonists, and that this site is distinct from that at which ketamine exerts its action. The action of Mg2+ is clearly different from that of either (-)-APV or ketamine. It is concluded that ketamine is a non-competitive antagonist of NMDA and may act at an allosteric site on the NMDA receptor complex to influence its function.

DrugBank Data that Cites this Article

Drugs

Ketamine

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Ketamine	Glutamate receptor ionotropic, NMDA 3A	Protein	Humans	Yes	Antagonist	Details