NMDA receptors are particularly important when they become overactive during, for example, withdrawal from alcohol as this causes symptoms such as agitation and, sometimes, epileptiform seizures.

Therefore, NMDA receptors will only open if glutamate is in the synapse and concurrently the postsynaptic membrane is already depolarized - acting as coincidence detectors at the neuronal level.

[8] The excitatory postsynaptic potential (EPSP) produced by activation of an NMDA receptor also increases the concentration of Ca2+ in the cell.

Examples of antagonists, or more appropriately named receptor channel blockers, of the NMDA receptor are APV, amantadine, dextromethorphan (DXM), ketamine, magnesium,[13] tiletamine, phencyclidine (PCP), riluzole, memantine, methoxetamine (MXE), methoxphenidine (MXP) and kynurenic acid.

While dizocilpine is generally considered to be the prototypical NMDA receptor blocker and is the most common agent used in research, animal studies have demonstrated some amount of neurotoxicity, which may or may not also occur in humans.