title: Allosteric modulators of NMDA receptors: multiple sites and mechanisms.
abstract: N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels that are essential mediators of excitatory neurotransmission and synaptic plasticity. NMDARs are also implicated in a plethora of neuropathological conditions thus receiving strong interest as potential therapeutic targets. Recent years have witnessed major progress in our understanding of the structure and pharmacology of NMDARs with the decoding of the first full-length receptor crystal structures and the discovery of allosteric modulators acting at novel binding sites and with unique patterns of subunit selectivity. Here we review the properties and structural mechanisms of various allosteric modulators that target NMDARs, emphasizing the newly identified compounds. The expanding pharmacology of NMDARs should help delineate the roles of various NMDAR subtypes in brain function, with potential for drug development.
authors.affiliation: Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS UMR 8197, INSERM U1024, 75005 Paris, France.
authors.forename: Shujia
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS UMR 8197, INSERM U1024, 75005 Paris, France. Electronic address: pierre.paoletti@ens.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Paoletti
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D001665:Binding Sites; D001921:Brain / Q000502:physiology / Q000503:physiopathology; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D009422:Nervous System Diseases / Q000188:drug therapy / Q000503:physiopathology*; D009473:Neuronal Plasticity / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate