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'.
MRC Centre for Synaptic Plasticity, School of Physiology and Pharmacology, University of Bristol, Bristol BS1 3NY, UK. G.L.Collingridge@bristol.ac.uk
Graham L
GL
Collingridge
Arturas
A
Volianskis
Neil
N
Bannister
Grace
G
France
Lydia
L
Hanna
Marion
M
Mercier
Patrick
P
Tidball
Guangyu
G
Fang
Mark W
MW
Irvine
Blaise M
BM
Costa
Daniel T
DT
Monaghan
Zuner A
ZA
Bortolotto
Elek
E
Molnár
David
D
Lodge
David E
DE
Jane
D000818:Animals; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018697:Nootropic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D058573:Performance-Enhancing Substances / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects
D009419:Nerve Tissue Proteins; D018697:Nootropic Agents; D058573:Performance-Enhancing Substances; D016194:Receptors, N-Methyl-D-Aspartate