The NMDA receptor as a target for cognitive enhancement

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'.