Abcam Biochemicals (formerly Ascent Scientific)

NMDA Product Range

NMDA Glutamate site
Glycine site
Ion Channel site
Polyamine site

NMDA receptors - @ a glance

NMDA receptors are heteromeric complexes incorporating different subunits of three different subtypes: GluN1, GluN2 and GluN3 (formerly NR1, NR2 and NR3). Variants of the GluN1 subunits are generated by alternative splicing from a single gene. The GluN2 and GluN3 subunits are encoded by six separate genes. There are eight different GluN1 variants. There are four different GluN2 variants: GluN2A, GluN2B, GluN2C and GluN2D (formerly NR2A, NR2B, NR2C, NR2D). There are two GluN3 variants: GluN3A and GluN3B (formerly known as NR3A and NR3B).

Functional mammalian NMDA receptors are tetrameric complexes most commonly comprised of two GluN1 and two GluN2 subunits of the same or different subtypes but one of the GluN2 subunits may be replaced by a GluN3 subunit. Tetrameric complexes comprised of GluN1/GluN3 activated solely by glycine have been expressed in mammalian cell lines but their existence in neurones has not been reported.

In addition to glutamate, the NMDA receptor requires a co-agonist, glycine, to bind to allow the receptor to function. The glycine binding site is found on the GluN1 subunit. The GluN2B subunit also posesses a binding site for ployamines, that modulate the functioning of the NMDA receptor. NMDA receptors have high relative permeability to Ca2+ and are blocked by Mg2+ in a voltage-dependent manner at resting potential.

NMDA receptor ligands - subunit selectivity

Receptor
GluN1 / GluN2A
GluN1 / GluN2B
GluN1 / GluN2D
GluN1 / GluN2D
References
Previous Nomenclature
NR1/NR2A
NR1/NR2B
NR1/NR2C
NR1/NR2D
 
Competitive antagonists (Ki values shown (μM))
D-AP5 0.3 0.5 1.6 3.7 Feng et al ...
(R)-CPP 0.04 0.3 0.6 2 Feng et al ...
7-Chlorokynurenic acid 0.6 0.2 0.1 0.6 Yamakura et al ...
5, 7-Dichlorokynurenic acid 0.03 0.05 0.2 0.09 Hess et al ...
UBP141 22 17.2 5.24 2.36 Costa et al ...
Channel blockers (IC50 values shown (μM))
(+)-MK 801 0.01 0.01 0.1   Yamakura et al ...
Memantine 0.9 0.01 ND?   Bresink et al ...
Allosteric inhibitors (IC50 values shown (μM))
Ifenprodil >30 0.15 >30 >30 Hess et al ...

Williams et al ...
Ro 25-6981 >30 0.04 >30 >30 Fischer et al ...

References

  1. Feng et al (2005) The effect of competitive antagonist chain length on NMDA receptor subunit selectivity. Neuropharmacol. 48:354
  2. Yamakura et al (1999) Subunit- and site-specific pharmacology of the NMDA receptor channel. Prog Neurobiol. 59:279-98
  3. Hess et al (1998) Functional characterization of human N-methyl-D-aspartate subtype 1A/2D receptors. J Neurochem. 70:1269-79
  4. Costa et al (2009) NMDA receptor NR2 subunit selectivity of a series of novel piperazine-2,3-dicarboxylate derivatives; preferential blockade of extrasynaptic NMDA receptors in the rat hippocampal CA3-CA1 synapse. JPET (In Press).
  5. Yamakura et al (1993) Different sensitivities of NMDA receptor channel subtypes to non-competitive antagonists. Neuroreport. 4:687-90
  6. Bresink et al (1996) Effects of memantine on recombinant rat NMDA receptors expressed in HEK 293 cells. Br J Pharmacol. 119:195-204
  7. Hess et al (1998) Functional characterization of human N-methyl-D-aspartate subtype 1A/2D receptors. J Neurochem. 70:1269-79
  8. Williams et al (1993) Ifenprodil discriminates subtypes of the N-methyl-D-aspartate receptor: selectivity and mechanisms at recombinant heteromeric receptors. Mol Pharmacol. 44:851-9
  9. Fischer et al (1997) Ro 25-6981, a highly potent and selective blocker of N-methyl-D-aspartate receptors containing the NR2B subunit. Characterization in vitro. J Pharmacol Exp Ther. 283:1285-92

NMDA receptor resources

For further information please see:
Glutamate receptors - @ a glance
Guide to Receptors and Channels. British Journal of Pharmacology: Ionotropic receptors
Recommended reviews from our technical team

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