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  Indian J Med Microbiol
 

Figure 1: (a) The tripartite glutamatergic synapse and potential drug targets. Left panel: The presynaptic neuron releases glutamate neurotransmitter in response to action potentials. The glutamate neurotransmitter can bind to ionotropic (i.e. NMDA, AMPA, kainate) and metabotropic (i.e mGluR) receptors located on the presynaptic and postsynaptic neuron as well as on astrocytes. Synaptic glutamate reuptake is performed primarily by the EAAT-2 located on astrocytes. Within the astrocyte, glutamate is converted to glutamine (glutamate/glutamine cycle) via glutamine transaminase (synthetase) and then resupplied to the presynaptic neuron where it is used for the biosynthesis of glutamate neurotransmitter. Right panel: Potential NMDA and EAAT-2 drug targets: (A) Noncompetitive NR2 subunits-unselective NMDA receptor antagonist (e.g. ketamine and memantine) and low-trapping NMDA receptor channel blockers (lanicemine [AZD6765]); (B) NR2B subunit-selective NMDA receptor antagonists (e.g. traxoprodil [CP-101,606] and MK-0657); (C) NR1 subunit-selective NMDA receptor partial agonists (e.g. GLYX-13 [Rapastinel], NRX- 1074 [Apimostinel], and D-cycloserine); (D) EAAT-2 reuptake enhancer (e.g. Riluzole). Abbreviations: NMDA, N-methyl-D-aspartate; AMPA, α-amino-3-hydroxy-5-methyl- 4-isoxazolepropionic acid; mGluR, metabotropic glutamate receptors; EAAT-2, excitatory amino acid transporter-2. (b) A schematic representation of the NMDA-glutamatergic receptor (NMDAR) heteromeric complex

Figure 1: (a) The tripartite glutamatergic synapse and potential drug targets. Left panel: The presynaptic neuron releases glutamate neurotransmitter in response to action potentials. The glutamate neurotransmitter can bind to ionotropic (i.e. NMDA, AMPA, kainate) and metabotropic (i.e mGluR) receptors located on the presynaptic and postsynaptic neuron as well as on astrocytes. Synaptic glutamate reuptake is performed primarily by the EAAT-2 located on astrocytes. Within the astrocyte, glutamate is converted to glutamine (glutamate/glutamine cycle) via glutamine transaminase (synthetase) and then resupplied to the presynaptic neuron where it is used for the biosynthesis of glutamate neurotransmitter. Right panel: Potential NMDA and EAAT-2 drug targets: (A) Noncompetitive NR2 subunits-unselective NMDA receptor antagonist (e.g. ketamine and memantine) and low-trapping NMDA receptor channel blockers (lanicemine [AZD6765]); (B) NR2B subunit-selective NMDA receptor antagonists (e.g. traxoprodil [CP-101,606] and MK-0657); (C) NR1 subunit-selective NMDA receptor partial agonists (e.g. GLYX-13 [Rapastinel], NRX- 1074 [Apimostinel], and D-cycloserine); (D) EAAT-2 reuptake enhancer (e.g. Riluzole). Abbreviations: NMDA, N-methyl-D-aspartate; AMPA, α-amino-3-hydroxy-5-methyl- 4-isoxazolepropionic acid; mGluR, metabotropic glutamate receptors; EAAT-2, excitatory amino acid transporter-2. (b) A schematic representation of the NMDA-glutamatergic receptor (NMDAR) heteromeric complex