The NMDA receptor is one of the main mediators of excitatory neurotransmission. The binding of both glutamate and glycine activates this receptor. The receptor is a ligand gated ion channel, which permits the movement of calcium, sodium and potassium across the post-synaptic membrane. The NMDA receptor is composed of the main NMDAR1 sub-unit and four additional sub-units – NMDA-R2A, NMDA-R2B, NMDA-R2C and NMDA-R2D sub-units.
The NMDA receptor can be modulated by a number of antagonists, including competitive antagonists at the glycine and glutamate binding sites and non-competitive NMDA receptor channel blockers. Since NMDA receptor activation is dependent on the binding of both glycine and glutamate, the binding of an antagonist at either of these sites prevents activation and opening of the channel.