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New basic and clinical research is clarifying the mechanistic relevance and therapeutic feasibility of multiple targets within the glutamate system for novel drug discovery, including NMDA and AMPA (-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors, metabotropic glutamate receptors, and other key regulatory proteins such as glycine transporter 1 and excitatory amino acid transporters