NMDA Receptors

NMDA receptors are members of the ionotropic class of glutamate receptors, which also includes Kainate and AMPA receptors. NMDA receptors are tetramers that consist of GluN1 subunits combined with GluN2 (A-D) or GluN3 (A-B) subunits. These complex and unique receptors mediate excitatory synaptic transmission, in conjunction with AMPA receptors.

Literature (5)
Gene Data

NMDA Receptor Agonists

Cat. No. Product Name / Activity
3406 GLYX 13
NMDA partial agonist; acts at the glycine site
0281 (R)-(+)-HA-966
NMDA partial agonist/antagonist; acts at glycine site
0285 Ibotenic acid
NMDA agonist; also non selective mGlu agonist
0114 NMDA
Selective NMDA agonist
0312 (RS)-(Tetrazol-5-yl)glycine
Highly potent NMDA agonist

NMDA Receptor Antagonists

Cat. No. Product Name / Activity
3693 DL-AP5 Sodium salt
Potent and selective NMDA antagonist; sodium salt of DL-AP5
0106 D-AP5
Potent and selective NMDA receptor antagonist; more active form of DL-AP5
0105 DL-AP5
Potent and selective NMDA antagonist
0107 L-AP5
Potent and selective NMDA antagonist; less active form of DL-AP5
4492 Cerestat
Potent and noncompetitive NMDA antagonist
1469 CGP 37849
Potent and selective NMDA antagonist
1409 CGP 39551
Potent, selective and competitive NMDA antagonist
1493 CGP 78608 hydrochloride
Potent and selective NMDA antagonist; acts at glycine site
1241 CGS 19755
Potent competitive NMDA antagonist
3697 7-Chlorokynurenic acid sodium salt
Sodium salt of 7-Chlorokynurenic acid
0237 7-Chlorokynurenic acid
NMDA antagonist; acts at glycine site
0190 CNQX
NMDA antagonist; acts at glycine site; also AMPA/kainate antagonist
2456 Co 101244 hydrochloride
GluN2B-selective NMDA antagonist
0247 (R)-CPP
Potent NMDA antagonist; more active enantiomer of (RS)-CPP
0173 (RS)-CPP
Potent NMDA antagonist
1265 D-CPP-ene
Potent competitive NMDA antagonist
0286 5,7-Dichlorokynurenic acid
Potent NMDA antagonist; acts at glycine site
3698 5,7-Dichlorokynurenic acid sodium salt
Potent NMDA antagonist, acts at glycine site; sodium salt of 5,7-Dichlorokynurenic acid
4491 DQP 1105
GluN2C/GluN2D-selective NMDA antagonist
2867 Flupirtine maleate
Indirect NMDA antagonist; also GABAA modulator and Kv7 channel activator
2348 Gavestinel
Potent and selective NMDA antagonist; acts at the glycine site
0545 Ifenprodil hemitartrate
Non-competitive NMDA antagonist; also σ ligand
3131 Ketamine hydrochloride
Non-competitive NMDA antagonist
6751 (R)-(-)-Ketamine hydrochloride
NMDA antagonist; antidepressant; may not display psychotomimetic or addictive side effects of (S)-ketamine
4379 (S)-(+)-Ketamine hydrochloride
NMDA antagonist; enantiomer of ketamine hydrochloride
0742 L-689,560
Highly potent NMDA antagonist
0705 L-701,252
NMDA antagonist; acts at glycine site
0907 L-701,324
NMDA antagonist; acts at glycine site
0840 Loperamide hydrochloride
NMDA antagonist; reduces Ca2+ flux
0773 Memantine hydrochloride
NMDA antagonist; acts at ion channel site
0924 (+)-MK 801 maleate
Non-competitive NMDA antagonist; acts at ion channel site
0955 (-)-MK 801 maleate
NMDA antagonist; less active enantiomer of (+)-MK 801
1970 Norketamine hydrochloride
Potent non-competitive NMDA antagonist; antinociceptive
5018 PEAQX tetrasodium salt
Potent and GluN2A-selective NMDA antagonist
2557 Phencyclidine hydrochloride
Non-competitive NMDA antagonist
2530 PPDA
GluN2C/GluN2D-selective NMDA antagonist
4801 QNZ 46
Non-competitive and GluN2C/GluN2D-selective NMDA antagonist
1594 Ro 25-6981 maleate
GluN2B-selective NMDA antagonist
3254 Ro 61-8048
NMDA antagonist; increases kynurenic acid levels
1250 SDZ 220-581
Competitive NMDA antagonist
4154 TCN 201
GluN1/GluN2A-selective NMDA antagonist

NMDA Receptor Modulators

Cat. No. Product Name / Activity
4105 CIQ
Potentiator of NMDA receptors containing GluN2C/GluN2D
0219 Glycine
Endogenous potentiator of NMDA receptors
6369 GNE 9278
Positive allosteric modulator of NMDA receptors; acts in transmembrane domain
2851 Nefiracetam
Cognitive enhancer; potentiates NMDA currents
5996 (R)-Norketamine hydrochloride
NMDA modulator; metabolite of Ketamine hydrochloride
6112 (S)-Norketamine hydrochloride
NMDA modulator; metabolite of Ketamine hydrochloride
1067 Oxotremorine M
Potentiator of NMDA receptors; also muscarinic M1 agonist
5376 Pregnenolone sulfate sodium salt
NMDA potentiator; also GABAA inhibitor and TRPM3 activator
0226 D-Serine
Potentiator of NMDA recepors; acts at glycine site


Cat. No. Product Name / Activity
6095 2S,6S-Hydroxynorketamine hydrochloride
Ketamine metabolite; decreases D-serine (a NMDA co-agonist); antidepressant
1636 IEM 1460
Open-channel blocker of NMDA currents; also blocks AMPA currents
0958 Spermine tetrahydrochloride
Modulator at polyamine site

NMDA receptors are expressed alongside AMPA receptors on the postsynaptic membrane of excitatory synapses, where they initiate a two-component excitatory postsynaptic potential (EPSP). The activation of AMPA receptors produces a current that has rapid onset and decay, while activation of NMDA receptors leads to a current with slower onset and decay. The slow decay of NMDA-mediated currents is due to the slow dissociation of glutamate from NMDA receptors, compared with AMPA receptors. Unlike other ionotropic glutamate receptors, NMDA receptors are highly permeable to Ca2+.

NMDA Receptor Structure

NMDA receptors are heteromeric tetramers, with every endogenously expressed NMDA receptor containing at least one GluN1 subunit, in combination with one or more GluN2 or GluN3 subunits. There is high variability in the exact subunit combination of endogenous NMDA receptors, as there have been 9 splice variants of GluN1 identified, as well as four genes for GluN2 (A to D) and two genes for GluN3 (A and B). The exact subunit conformation of a NMDA receptor determines the ability of the receptor to bind different ligands and the Ca2+ permeability of the receptor.

During postnatal development the subunit combinations expressed in the brain change. In early postnatal development, NMDA receptors are primarily composed of N1 and N2B subunits, resulting in very long-lasting synaptic responses. However, during the first weeks of brain development, the N2B subunit is replaced with N2A or N2C, leading to a shorter synaptic response.

Unique features of NMDA Receptors

NMDA receptors have properties that set them apart from other ligand-gated ion channels:

  • divalent cation block
  • multiple ligands required for activation
  • a third pharmacological binding site within the ion pore

At resting membrane potentials, extracellular Mg2+ and Zn2+ block the ion pore of NMDA receptors, so that even in the presence of glutamate there is very little ion flow. Depolarization of the postsynaptic membrane where NMDA receptors are expressed is required to remove this block. Repetitive stimulation of the postsynaptic neuron is required to relieve the Mg2+/Zn2+ block, suggesting that NMDA receptors can detect simultaneous activity at adjacent receptors on the synaptic membrane. However, this sustained activation of the postsynaptic membrane can lead to glutamate excitotoxicity, due to the large influx of Ca2+ through extrasynaptic NMDA receptors. This has been postulated as a cause of cell death in neurogenerative diseases, such as Alzheimer's disease and Parkinson's disease.

Another unique feature of NMDA receptors is the requirement for two ligands to bind for endogenous activation. Both glutamate and glycine are required to bind at their respective binding sites. These ligands are referred to as co-agonists, and neither can activate the receptor without the other. Both the glutamate and glycine binding sites are targets for drugs. D-serine can also activate NDMA receptors with glutamate by binding to the glycine binding site; it is more potent than glycine. D-serine is released from glial cells in the CNS, suggesting a critical role for glial cells in modulating NMDA synaptic function.

The third unique feature of NMDA receptors is the presence of a third pharmacological binding site, within the ion pore near the Mg2+/Zn2+ blocking point. Drugs that bind at this site, such as MK 801 and Ketamine, physically block ion flow through the ion channel pore, and are described as non-competitive antagonists. At lower concentrations these compounds are psychotomimetic causing cognitive impairments, hallucinations and delusions, while at higher concentrations they are dissociative anesthetics.

External sources of pharmacological information for NMDA Receptors :

Literature for NMDA Receptors

Tocris offers the following scientific literature for NMDA Receptors to showcase our products. We invite you to request* your copy today!

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NMDA Receptor Gene Data

Gene Species Gene Symbol Gene Accession No. Protein Accession No.
GluN1 Human GRIN1 NM_021569 Q05586
Mouse Grin1 NM_008169 P35438
Rat Grin1 NM_017010 P35439
GluN2A Human GRIN2A NM_000833 Q12879
Mouse Grin2a NM_008170 P35436
Rat Grin2a NM_012573 Q00959
GluN2B Human GRIN2B NM_000834 Q13224
Mouse Grin2b NM_008171 Q01097
Rat Grin2b NM_012574 Q00960
GluN2C Human GRIN2C NM_000835 Q14957
Mouse Grin2c NM_010350 Q01098
Rat grin2c NM_012575 Q00961
GluN2D Human GRIN2D NM_000836 O15399
Mouse Grin2d NM_008172 Q03391
Rat Grin2d NM_022797 Q62645
GluN3A Human GRIN3A NM_133445 Q8TCU5
Mouse Grin3a NM_001033351 NP_001028523
Rat Grin3a AF073379 Q9R1M7
GluN3B Human GRIN3B NM_138690 O60391
Mouse Grin3b NM_130455 Q91ZU9
Rat Grin3b NM_133308 Q8VHN2