Positive and Negative Allosteric Modulators of N-Methyl-d-aspartate (NMDA) Receptors: Structure-Activity Relationships and Mechanisms of Action.
Positive and Negative Allosteric Modulators of N-Methyl-d-aspartate (NMDA) Receptors: Structure-Activity Relationships and Mechanisms of Action.
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DOI：
10.1021/acs.jmedchem.7b01640
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发表时间：
2019-01-10
影响因子：
7.3
通讯作者：
Monaghan DT
中科院分区：
文献类型：
--
作者：
Burnell ES;Irvine M;Fang G;Sapkota K;Jane DE;Monaghan DT
CNS 中的兴奋活动主要由 L-谷氨酸通过几个 L-谷氨酸神经递质受体家族介导。其中，N-甲基-D-天冬氨酸受体 (NMDAR) 家族在中枢神经系统功能以及各种神经病理学和精神疾病中具有许多关键作用。直到最近，可用于调节 NMDAR 功能的化合物类型在作用机制、亚型选择性和生物效应方面还相当有限。然而，现已鉴定出几种新型 NMDAR 药物，它们是具有各种 NMDAR 亚型选择性模式的正向或负向变构调节剂（分别为 PAM 和 NAM）。这些新药物作用于 NMDAR 复合物上几个新识别的结合位点，并且比以前可用的药物对 NMDAR 活性提供显着更强的药理学控制。本综述的目的是总结这些新型 NMDAR 调节剂药物类别的结构-活性关系，并描述目前对其作用机制的理解。
Excitatory activity in the CNS is predominately mediated by L-glutamate through several families of L-glutamate neurotransmitter receptors. Of these, the N-methyl-D-aspartate receptor (NMDAR) family has many critical roles in CNS function and in various neuropathological and psychiatric conditions. Until recently, the types of compounds available to regulate NMDAR function have been quite limited in terms of mechanism of action, subtype selectivity, and biological effect. However, several new classes of NMDAR agents have now been identified that are positive or negative allosteric modulators (PAMs and NAMs, respectively) with various patterns of NMDAR subtype selectivity. These new agents act at several newly recognized binding sites on the NMDAR complex and offer significantly greater pharmacological control over NMDAR activity than previously available agents. The purpose of this review is to summarize the structure-activity relationships for these new NMDAR modulator drug classes and to describe the current understanding of their mechanisms of action.
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影响因子：
4.6
作者：
Chopra DA;Sapkota K;Irvine MW;Fang G;Jane DE;Monaghan DT;Dravid SM
通讯作者：
Dravid SM
影响因子：
7.3
作者：
Irvine, Mark W.;Costa, Blaise M.;Jane, David E.
通讯作者：
Jane, David E.
影响因子：
5.5
作者：
BENVENISTE, M;MAYER, ML
通讯作者：
MAYER, ML
影响因子：
3.3
作者：
Horak, M;Vlcek, K;Vyklicky, L
通讯作者：
Vyklicky, L
影响因子：
4.6
作者：
Bu, Fan;Du, Ruoxing;Wang, Minyan
通讯作者：
Wang, Minyan