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Overview
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Background
NMDA is an agonist of NMDA-receptor [1].NMDA is a glutamate-like excitatory substance and is a particularly potent excitant. NMDA binds to NMDA-receptor and interacts with it. This interaction causes a conformational change in the receptor or associated membrane molecules, which opened pores to allow extracellular sodium ions to flow down their electrochemical gradient and depolarise the cell. However, NMDA is proved to be a poor substrate for the uptake transporters, suggesting that the excitatory effect could not be an indirect consequence of glutamate uptake. Besides that, NMDA is found to increase intracellular calcium and release arachidonic acid, both of which generate oxygen radicals, subsequently inducing neuronal death [1, 2].
[1] Watkins JC, Jane DE. The glutamate story. Br J Pharmacol. 2006 Jan;147 Suppl 1:S100-8.
[2] Lafon-Cazal M, Pietri S, Culcasi M, Bockaert J. NMDA-dependent superoxide production and neurotoxicity. Nature. 1993 Aug 5;364(6437):535-7.
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Overview