MRC Centre for Synaptic Plasticity, School of Physiology and Pharmacology, University of Bristol, Bristol BS1 3NY, UK.
Neuropharmacology. 2013 Jan;64:13-26. doi: 10.1016/j.neuropharm.2012.06.051. Epub 2012 Jul 11.
NMDA receptors (NMDARs) play an important role in neural plasticity including long-term potentiation and long-term depression, which are likely to explain their importance for learning and memory. Cognitive decline is a major problem facing an ageing human population, so much so that its reversal has become an important goal for scientific research and pharmaceutical development. Enhancement of NMDAR function is a core strategy toward this goal. In this review we indicate some of the major ways of potentiating NMDAR function by both direct and indirect modulation. There is good evidence that both positive and negative modulation can enhance function suggesting that a subtle approach correcting imbalances in particular clinical situations will be required. Excessive activation and the resultant deleterious effects will need to be carefully avoided. Finally we describe some novel positive allosteric modulators of NMDARs, with some subunit selectivity, and show initial evidence of their ability to affect NMDAR mediated events. This article is part of a Special Issue entitled 'Cognitive Enhancers'.
N-甲基-D-天冬氨酸受体（NMDARs）在神经可塑性中发挥重要作用，包括长时程增强和长时程抑制，这可能解释了它们在学习和记忆中的重要性。认知能力下降是老龄化人口面临的主要问题，因此，逆转认知能力下降已成为科学研究和药物开发的重要目标。增强 NMDAR 功能是实现这一目标的核心策略。在这篇综述中，我们通过直接和间接调节指出了增强 NMDAR 功能的一些主要方法。有充分的证据表明，正性和负性调节都可以增强功能，这表明在特定的临床情况下，需要采取微妙的方法来纠正失衡。需要谨慎避免过度激活和由此产生的有害影响。最后，我们描述了一些具有某些亚基选择性的新型 NMDAR 正变构调节剂，并展示了它们影响 NMDAR 介导事件的初步证据。本文是特刊“认知增强剂”的一部分。
