Activation of NMDA receptors by glutamate and other excitatory amino acids enhances calcium and sodium flow into neurons, with a resultant increase in excitatory postsynaptic potentials. NMDA receptors contain four subunits: two NR1 and two NR2 subunits. NR2A and NR2B subtypes exist, and, in some cases, other subunits, such as the NR3 subunit, may also be present. Glutamate may activate NMDA receptors by binding to the NR2 or comparable subunit. The functioning of NMDA receptors is dependent on the binding of the amino acid glycine to the NR1 subunit. NMDA receptor–mediated flux is regulated by a voltage-dependent magnesium block. Consequently, these receptors become active only when a certain level of neuronal depolarization is reached. Competitive antagonists directly block the binding of glutamate to the NMDA receptor. Ketamine, phencyclidine, and many other agents act as uncompetitive antagonists at the NMDA receptor by binding to sites within the ion channel of the receptor complex.