Zhu Shujia, Paoletti Pierre
Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS UMR 8197, INSERM U1024, 75005 Paris, France.
Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS UMR 8197, INSERM U1024, 75005 Paris, France.
Curr Opin Pharmacol. 2015 Feb;20:14-23. doi: 10.1016/j.coph.2014.10.009. Epub 2014 Nov 12.
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.
N-甲基-D-天冬氨酸受体（NMDARs）是谷氨酸门控离子通道，是兴奋性神经传递和突触可塑性的重要介质。NMDARs还与多种神经病理状况有关，因此作为潜在的治疗靶点备受关注。近年来，随着首个全长受体晶体结构的解析以及作用于新结合位点且具有独特亚基选择性模式的变构调节剂的发现，我们对NMDARs的结构和药理学的理解取得了重大进展。在此，我们综述了靶向NMDARs的各种变构调节剂的特性和结构机制，重点介绍新发现的化合物。NMDARs不断扩展的药理学应有助于阐明各种NMDAR亚型在脑功能中的作用，具有药物开发潜力。
