NMD
A receptors (NMDARs) pl
ay
an import
ant role in neur
al pl
asticity including long-term potenti
ation
and long-term depression, which
are likely to expl
ain their import
ance for le
arning
and memory. Cognitive decline is
a m
ajor problem f
acing
an
ageing hum
an popul
ation, so much so th
at its revers
al h
as become
an import
ant go
al for scientific rese
arch
and ph
arm
aceutic
al development. Enh
ancement of NMDAR function is
a core str
ategy tow
ard this go
al. In this review we indic
ate some of the m
ajor w
ays of potenti
ating NMDAR function by both direct
and indirect modul
ation. There is good evidence th
at both positive
and neg
ative modul
ation c
an enh
ance function suggesting th
at
a subtle
appro
ach correcting imb
al
ances in p
articul
ar clinic
al situ
ations will be required. Excessive
activ
ation
and the result
ant deleterious effects will need to be c
arefully
avoided. Fin
ally we describe some novel positive
allosteric modul
ators of NMDARs, with some subunit selectivity,
and show initi
al evidence of their
ability to
affect NMDAR medi
ated events.
This article is part of a Special Issue entitled ¡®Cognitive Enhancers¡¯.