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α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)受体增强剂:从药物设计到认知增强

AMPA receptor potentiators: from drug design to cognitive enhancement.

作者信息

Partin Kathryn M

机构信息

Department of Biomedical Sciences, Colorado State University, Fort Collins, Co 80523-1617, United States.

出版信息

Curr Opin Pharmacol. 2015 Feb;20:46-53. doi: 10.1016/j.coph.2014.11.002. Epub 2014 Nov 27.

Abstract

Positive allosteric modulators of ionotropic glutamate receptors have emerged as a target for treating cognitive impairment and neurodegeneration, but also mental illnesses such as major depressive disorder. The possibility of creating a new class of pharmaceutical agent to treat refractive mental health issues has compelled researchers to redouble their efforts to develop a safe, effective treatment for memory and cognition impairments. Coupled with the more robust research methodologies that have emerged, including more sophisticated high-throughput-screens, higher resolution structural biology techniques, and more focused assessment on pharmacokinetics, the development of positive modulators of AMPA receptors holds great promise. We describe recent approaches that improve our understanding of the basic physiology underlying memory and cognition, and their application toward promoting human health.

摘要

离子型谷氨酸受体的正向变构调节剂已成为治疗认知障碍、神经退行性变以及诸如重度抑郁症等精神疾病的靶点。研发一类新型药物来治疗难治性心理健康问题的可能性促使研究人员加倍努力,以开发出一种安全、有效的记忆和认知障碍治疗方法。再加上出现的更强大的研究方法,包括更精密的高通量筛选、更高分辨率的结构生物学技术以及对药代动力学更有针对性的评估,AMPA受体正向调节剂的开发前景广阔。我们描述了一些最新方法,这些方法增进了我们对记忆和认知基础基本生理学的理解,以及它们在促进人类健康方面的应用。

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引用本文的文献

本文引用的文献

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The multifaceted subunit interfaces of ionotropic glutamate receptors.离子型谷氨酸受体的多面亚基界面。
J Physiol. 2015 Jan 1;593(1):73-81. doi: 10.1113/jphysiol.2014.273409. Epub 2014 Jul 10.
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Pharmacological enhancement of memory or cognition in normal subjects.正常受试者记忆或认知的药理学增强。
Front Syst Neurosci. 2014 May 20;8:90. doi: 10.3389/fnsys.2014.00090. eCollection 2014.
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Functional insight into development of positive allosteric modulators of AMPA receptors.对AMPA受体正变构调节剂开发的功能洞察
Neuropharmacology. 2014 Oct;85:57-66. doi: 10.1016/j.neuropharm.2014.05.022. Epub 2014 May 27.
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AMPARs and synaptic plasticity: the last 25 years.AMPA 受体与突触可塑性:过去 25 年。
Neuron. 2013 Oct 30;80(3):704-17. doi: 10.1016/j.neuron.2013.10.025.

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