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N-methyl-D-aspartate (NMDA) receptor antagonists and modulators act on glutamate-gated ion channels in neurons. NMDA receptors take part in excitatory synaptic transmission, synaptic plasticity and excitotoxicity. The first NMDA receptor subunit was cloned from rat brain in 1991. Extracellular magnesium blocks the channel in a voltage-dependent manner, so activation requires both agonist binding and membrane depolarization. The category includes the agonist NMDA itself, the channel blocker memantine hydrochloride and the competitive antagonist SDZ 220-581. Subunit-selective tools include TCN 201, a negative allosteric modulator of GluN2A-containing receptors, and GNE 0723, a positive allosteric modulator of the same receptors.
