NMDA receptors (NMDARs) are glutamate-gated ion channels expressed in the central nervous system and play key roles in excitatory synaptic transmission. They are targets for therapeutic interest due to their involvement in various neurological disorders. NMDARs exist as multiple subtypes with distinct subunit compositions and pharmacological properties. Recent structural and functional studies have revealed molecular determinants for subunit-selective modulation, including binding sites for glutamate, the ion-channel pore, and allosteric sites on the N-terminal domain. These findings highlight the pharmacological heterogeneity of NMDARs and their potential for developing subtype-selective compounds. NMDAR subtypes such as NR2B are implicated in pain, while NR3A is involved in white matter injury. The functional diversity of NMDAR subtypes has led to increased interest in subtype-selective pharmacological agents. NMDARs are heteromeric complexes composed of NR1, NR2, and NR3 subunits. The molecular organization of NMDARs includes extracellular and cytoplasmic domains, with the N-terminal domain (NTD) playing a role in subunit assembly and binding of allosteric modulators. The agonist-binding domain (ABD) is crucial for receptor activation, requiring the simultaneous binding of glutamate and glycine. Structural studies have elucidated the mechanisms of NMDAR activation, including the role of subunit dimerization and the influence of subunit composition on receptor function. Pharmacological studies have identified various compounds that act at different sites of NMDARs, including competitive antagonists, pore blockers, and allosteric modulators. These compounds exhibit varying degrees of subunit selectivity, with some showing high specificity for NR2B or NR3A subunits. The development of subtype-selective NMDAR antagonists has been a focus of research, with recent advances in understanding the molecular mechanisms underlying subunit-specific modulation. NMDARs are also expressed in glial cells, such as oligodendrocytes, and their dysfunction is implicated in neurological disorders. The therapeutic potential of NMDARs as targets for drug development is significant, particularly in the treatment of schizophrenia and other neurological conditions. The identification of subtype-selective modulators and the understanding of their mechanisms of action are crucial for the development of novel therapeutic agents.NMDA receptors (NMDARs) are glutamate-gated ion channels expressed in the central nervous system and play key roles in excitatory synaptic transmission. They are targets for therapeutic interest due to their involvement in various neurological disorders. NMDARs exist as multiple subtypes with distinct subunit compositions and pharmacological properties. Recent structural and functional studies have revealed molecular determinants for subunit-selective modulation, including binding sites for glutamate, the ion-channel pore, and allosteric sites on the N-terminal domain. These findings highlight the pharmacological heterogeneity of NMDARs and their potential for developing subtype-selective compounds. NMDAR subtypes such as NR2B are implicated in pain, while NR3A is involved in white matter injury. The functional diversity of NMDAR subtypes has led to increased interest in subtype-selective pharmacological agents. NMDARs are heteromeric complexes composed of NR1, NR2, and NR3 subunits. The molecular organization of NMDARs includes extracellular and cytoplasmic domains, with the N-terminal domain (NTD) playing a role in subunit assembly and binding of allosteric modulators. The agonist-binding domain (ABD) is crucial for receptor activation, requiring the simultaneous binding of glutamate and glycine. Structural studies have elucidated the mechanisms of NMDAR activation, including the role of subunit dimerization and the influence of subunit composition on receptor function. Pharmacological studies have identified various compounds that act at different sites of NMDARs, including competitive antagonists, pore blockers, and allosteric modulators. These compounds exhibit varying degrees of subunit selectivity, with some showing high specificity for NR2B or NR3A subunits. The development of subtype-selective NMDAR antagonists has been a focus of research, with recent advances in understanding the molecular mechanisms underlying subunit-specific modulation. NMDARs are also expressed in glial cells, such as oligodendrocytes, and their dysfunction is implicated in neurological disorders. The therapeutic potential of NMDARs as targets for drug development is significant, particularly in the treatment of schizophrenia and other neurological conditions. The identification of subtype-selective modulators and the understanding of their mechanisms of action are crucial for the development of novel therapeutic agents.