Figure 3.

NitroMemantine-mediated inhibition of hyperactivated NMDA receptors. NitroMemantine was synthesized by addition of a nitro group (-NO₂) to the memantine moiety. This allows NitroMemantine to antagonize excessively activated NMDA receptors via two sites of action: 1) the ion channel where memantine itself binds, and 2) an extracellular redox-sensitive cysteine thiol groups of the receptor where the nitro group reacts to inhibit NMDAR activity (forming –SNO or –SNO₂). Thus, in this scenario, NitroMemantine serves as an NO (or, more precisely, a nitro group) donor specifically targeting NMDA receptors. This figure also shows that the NMDA receptor is a heterodimer, composed of two GluN1 and two GluN2 subunits. Excessive concentrations of glycine (Gly) and glutamate (Glu), co-agonists of the receptor, can trigger pathological activation of the NMDA receptor.