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mGlu2 receptor

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Target not currently curated in GtoImmuPdb

Target id: 290

Nomenclature: mGlu2 receptor

Family: Metabotropic glutamate receptors

Contents:

Gene and Protein Information Click here for help
class C G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 872 3p21.2 GRM2 glutamate metabotropic receptor 2 21,37
Mouse 7 872 9 F1 Grm2 glutamate receptor, metabotropic 2
Rat 7 872 8q32 Grm2 glutamate metabotropic receptor 2 53
Previous and Unofficial Names Click here for help
mGluR2 | GPRC1B | metabotropic glutamate receptor 2 | glutamate receptor
Database Links Click here for help
Specialist databases
GPCRdb grm2_human (Hs), grm2_mouse (Mm), grm2_rat (Rn)
Other databases
Alphafold Q14416 (Hs), Q14BI2 (Mm), P31421 (Rn)
ChEMBL Target CHEMBL5137 (Hs), CHEMBL2851 (Rn)
Ensembl Gene ENSG00000164082 (Hs), ENSMUSG00000023192 (Mm), ENSRNOG00000013171 (Rn)
Entrez Gene 2912 (Hs), 108068 (Mm), 24415 (Rn)
Human Protein Atlas ENSG00000164082 (Hs)
KEGG Gene hsa:2912 (Hs), mmu:108068 (Mm), rno:24415 (Rn)
OMIM 604099 (Hs)
Pharos Q14416 (Hs)
RefSeq Nucleotide NM_000839 (Hs), NM_001160353 (Mm), NM_001105711 (Rn)
RefSeq Protein NP_000830 (Hs), NP_001153825 (Mm), NP_001099181 (Rn)
UniProtKB Q14416 (Hs), Q14BI2 (Mm), P31421 (Rn)
Wikipedia GRM2 (Hs)
Natural/Endogenous Ligands Click here for help
L-glutamic acid
Comments: Other endogenous ligands include L-aspartic acid, L-serine-O-phosphate, NAAG and L-cysteine sulphinic acid

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Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]eglumegad Small molecule or natural product Ligand is labelled Ligand is radioactive Ligand has a PDB structure Rn Full agonist 7.7 pKd 51
⤷ pKd 7.7 [51]
MGS0028 Small molecule or natural product Rn Full agonist 9.2 pKi 39
⤷ pKi 9.2 [39]
LY379268 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.9 pKi 38
⤷ pKi 7.9 [38]
eglumegad Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Full agonist 7.8 – 7.9 pKi 9,51
⤷ pKi 7.8 – 7.9 [9,51]
DCG-IV Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Full agonist 7.0 pKi 9,51
⤷ pKi 7.0 [9,51]
L-CCG-I Small molecule or natural product Click here for species-specific activity table Rn Full agonist 6.8 – 7.0 pKi 9,51
⤷ pKi 6.8 – 7.0 [9,51]
eglumegad Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 6.9 pKi 24
⤷ pKi 6.9 [24]
LY395756 Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.8 pKi 32
⤷ pKi 6.8 (Ki 1.65x10-7 M) [32]
DCG-IV Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 6.5 pKi 24
⤷ pKi 6.5 [24]
L-CCG-I Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.3 pKi 24
⤷ pKi 6.3 [24]
L-glutamic acid Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Rn Full agonist 5.4 – 5.9 pKi 5,19
⤷ pKi 5.4 – 5.9 [5,19]
(1S,3R)-ACPD Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Full agonist 5.0 – 5.4 pKi 9,51
⤷ pKi 5.0 – 5.4 [9,51]
(2R,3R)-APDC Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 5.0 pKi 24
⤷ pKi 5.0 [24]
L-glutamic acid Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Full agonist 4.9 pKi 24
⤷ pKi 4.9 [24]
(S)-4C3HPG Small molecule or natural product Click here for species-specific activity table Rn Full agonist 4.8 pKi 9
⤷ pKi 4.8 [9]
(1S,3R)-ACPD Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 4.2 pKi 24
⤷ pKi 4.2 [24]
L-glutamic acid Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Agonist 4.7 – 5.4 pEC50 45
⤷ pEC50 4.7 – 5.4 [45]
View species-specific agonist tables
Agonist Comments
Affinities listed are from displacement of antagonist [3H]LY341495 or agonist ([3H]DCG-IV or [3H]LY354740) for the low and high values listed, respectively, in homogenates from mGlu2-expressing recombinant cell lines. Potency in functional assays can be found in the review article [50]. To date, no ligands have shown a difference in their affinity for rat or human mGlu2 receptors. Several of the above agonists are Group II mGlu (mGlu2/3) receptor selective verses the Group I and III receptors, with the exceptions of glutamate, (1S,3R)-ACPD, and (S)-4C3HPG. The agonist binding site for mGLu2 has been studied by homology modeling and mutagenesis [3,36].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]LY341495 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Antagonist 8.8 pKd 24
⤷ pKd 8.8 [24]
MGS0039 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 8.6 – 8.7 pKi 10,40
⤷ pKi 8.6 – 8.7 [10,40]
LY341495 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.6 pKi 24
⤷ pKi 8.6 [24]
LY341495 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 7.7 – 9.0 pKi 9,51
⤷ pKi 7.7 – 9.0 [9,51]
α-methylserine-O-phosphate Small molecule or natural product Click here for species-specific activity table Rn Antagonist 5.3 pKi 9
⤷ pKi 5.3 [9]
(+)-MCPG Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 4.6 pKi 9
⤷ pKi 4.6 [9]
eGlu Small molecule or natural product Click here for species-specific activity table Rn Antagonist 4.4 – 4.6 pKi 9,51
⤷ pKi 4.4 – 4.6 [9,51]
(+)-MCPG Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 3.8 pKi 24
⤷ pKi 3.8 [24]
PCCG-4 Small molecule or natural product Rn Antagonist 5.1 pIC50 43
⤷ pIC50 5.1 (IC50 8x10-6 M) [43]
View species-specific antagonist tables
Antagonist Comments
Affinities listed are from displacement of antagonist [3H]LY341495 and/or agonist ([3H]DCG-IV or [3H]LY354740) in homogenates of mGlu2-expressing recombinant cell lines. Potency in functional assays can be found in the review article [50]. To date, no ligands have shown a difference in their affinity for rat or human mGlu2 receptors.
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
JNJ-46281222 Small molecule or natural product Primary target of this compound Hs Positive 8.8 pKd 16
⤷ pKd 8.8 (Kd 1.7x10-9 M) [16]
Description: Saturation binding experiment using tritiated compound, and membranes from CHO-K1 cells stably expressing the human mGlu2 receptor.
[3H]2,2,2-TEMPS Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Positive 8.4 pKd 34
⤷ pKd 8.4 (Kd 4.2x10-9 M) [34]
[3H]JNJ-40068782 Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Positive 8.0 pKd 31
⤷ pKd 8.0 (Kd 1x10-8 M) [31]
[3H]JNJ-40068782 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Positive 7.9 pKd 31
⤷ pKd 7.9 (Kd 1.2x10-8 M) [31]
RO4988546 Small molecule or natural product Rn Negative 8.6 pKi 34
⤷ pKi 8.6 (Ki 2.3x10-9 M) [34]
RO5488608 Small molecule or natural product Rn Negative 7.9 – 8.7 pKi 34
⤷ pKi 7.9 – 8.7 (Ki 1.14x10-8 – 1.9x10-9 M) [34]
JNJ-46281222 Small molecule or natural product Primary target of this compound Hs Positive 8.3 pKi 16
⤷ pKi 8.3 (Ki 4.68x10-9 M) [16]
Description: Homologous displacement assay.
Ro4491533 Small molecule or natural product Click here for species-specific activity table Rn Negative 8.3 pKi 8
⤷ pKi 8.3 (Ki 5.4x10-9 M) [8]
JNJ-42153605 Small molecule or natural product Hs Positive 7.8 pKi 12
⤷ pKi 7.8 (Ki 1.5x10-8 M) [12]
Ro4491533 Small molecule or natural product Click here for species-specific activity table Hs Negative 6.4 – 8.2 pKi 8
⤷ pKi 6.4 – 8.2 (Ki 3.64x10-7 – 6.2x10-9 M) [8]
compound 3 [PMID: 21105727] Small molecule or natural product Click here for species-specific activity table Hs Negative 6.2 pKi 49
⤷ pKi 6.2 (Ki 6x10-7 M) [49]
compound 4 [PMID: 21105727] Small molecule or natural product Click here for species-specific activity table Hs Negative 6.1 pKi 49
⤷ pKi 6.1 (Ki 8x10-7 M) [49]
compound 2 [PMID: 21105727] Small molecule or natural product Click here for species-specific activity table Hs Negative 6.0 pKi 49
⤷ pKi 6.0 (Ki 1x10-6 M) [49]
THIIC Small molecule or natural product Rn Positive 7.9 pEC50 20
⤷ pEC50 7.9 (EC50 1.28x10-8 M) [20]
2,2,2-TEMPS Small molecule or natural product Hs Positive 7.8 pEC50 2
⤷ pEC50 7.8 (EC50 1.4x10-8 M) [2]
JNJ-42153605 Small molecule or natural product Hs Positive 7.8 pEC50 12
⤷ pEC50 7.8 (EC50 1.7x10-8 M) [12]
THIIC Small molecule or natural product Hs Positive 7.7 pEC50 20
⤷ pEC50 7.7 (EC50 2.25x10-8 M) [20]
compound 14a [PMID: 18812259] Small molecule or natural product Rn Positive 7.6 pEC50 56
⤷ pEC50 7.6 (EC50 2.6x10-8 M) [56]
cyPPTS Small molecule or natural product Hs Positive 7.6 pEC50 26
⤷ pEC50 7.6 (EC50 2.4x10-8 M) [26]
compound 14c [PMID: 18812259] Small molecule or natural product Rn Positive 7.5 pEC50 56
⤷ pEC50 7.5 (EC50 3x10-8 M) [56]
JNJ-40068782 Small molecule or natural product Hs Positive 6.8 – 7.8 pEC50 31
⤷ pEC50 6.8 – 7.8 (EC50 1.43x10-7 – 1.5x10-8 M) [31]
JNJ-40068782 Small molecule or natural product Rn Positive 7.3 pEC50 31
⤷ pEC50 7.3 (EC50 5.2x10-8 M) [31]
compound 19 [PMID: 18812259] Small molecule or natural product Rn Positive 7.2 pEC50 56
⤷ pEC50 7.2 (EC50 6.4x10-8 M) [56]
GSK1331258 Small molecule or natural product Hs Positive 7.1 pEC50 13
⤷ pEC50 7.1 (EC50 8x10-8 M) [13]
compound 34 [PMID: 20409708] Small molecule or natural product Hs Positive 7.1 pEC50 7
⤷ pEC50 7.1 (EC50 8.4x10-8 M) [7]
CBiPES Small molecule or natural product Hs Positive 7.0 pEC50 26
⤷ pEC50 7.0 (EC50 9.28x10-8 M) [26]
biphenylindanone A Small molecule or natural product Hs Positive 7.0 pEC50 4
⤷ pEC50 7.0 (EC50 1.11x10-7 M) [4]
GSK1331268 Small molecule or natural product Hs Positive 6.9 pEC50 13
⤷ pEC50 6.9 (EC50 1.25x10-7 M) [13]
JNJ-40411813 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Positive 6.8 pEC50 30
⤷ pEC50 6.8 (EC50 1.47x10-7 M) [30]
Description: Measured in a [35S]GTPγS binding assay with human metabotropic glutamate type 2 receptor expressed in CHO cells.
compound 14 [PMID: 21155570] Small molecule or natural product Rn Positive 6.8 pEC50 14
⤷ pEC50 6.8 (EC50 1.7x10-7 M) [14]
AZD8529 Small molecule or natural product Primary target of this compound Hs Positive 6.7 pEC50 1
⤷ pEC50 6.7 (EC50 1.95x10-7 M) [1]
compound 48 [PMID: 22364337] Small molecule or natural product Hs Positive 6.4 pEC50 11
⤷ pEC50 6.4 (EC50 3.61x10-7 M) [11]
4-APPES Small molecule or natural product Hs Positive 5.7 pEC50 26
⤷ pEC50 5.7 (EC50 2.26x10-6 M) [26]
RO4988546 Small molecule or natural product Rn Negative 8.3 pIC50 34
⤷ pIC50 8.3 (IC50 5.5x10-9 M) [34]
MNI-137 Small molecule or natural product Click here for species-specific activity table Rn Negative 7.7 – 8.1 pIC50 23
⤷ pIC50 7.7 – 8.1 (IC50 2.03x10-8 – 8.3x10-9 M) [23]
Ro4491533 Small molecule or natural product Click here for species-specific activity table Hs Negative 7.8 pIC50 54
⤷ pIC50 7.8 (IC50 1.4x10-8 M) [54]
MNI-136 Small molecule or natural product Hs Negative 7.3 – 8.1 pIC50 23
⤷ pIC50 7.3 – 8.1 (IC50 4.66x10-8 – 8.8x10-9 M) [23]
MNI-136 Small molecule or natural product Click here for species-specific activity table Rn Negative 7.7 – 7.7 pIC50 23
⤷ pIC50 7.7 – 7.7 (IC50 2.13x10-8 – 1.97x10-8 M) [23]
MNI-135 Small molecule or natural product Click here for species-specific activity table Rn Negative 7.5 – 7.7 pIC50 23
⤷ pIC50 7.5 – 7.7 (IC50 3.02x10-8 – 1.96x10-8 M) [23]
Ro4491533 Small molecule or natural product Click here for species-specific activity table Rn Negative 6.5 – 8.7 pIC50 8,54
⤷ pIC50 6.5 – 8.7 (IC50 2.96x10-7 – 2x10-9 M) [8,54]
MNI-137 Small molecule or natural product Hs Negative 7.1 – 7.9 pIC50 23
⤷ pIC50 7.1 – 7.9 (IC50 7.27x10-8 – 1.26x10-8 M) [23]
MNI-135 Small molecule or natural product Hs Negative 6.9 – 8.0 pIC50 23
⤷ pIC50 6.9 – 8.0 (IC50 1.18x10-7 – 1.05x10-8 M) [23]
Ro64-5229 Small molecule or natural product Rn Negative 7.0 pIC50 29
⤷ pIC50 7.0 (IC50 1.1x10-7 M) [29]
3-MPPTS Small molecule or natural product Hs Positive 6.6 pIC50 25-26,48
⤷ pIC50 6.6 [25-26,48]
PTBE Small molecule or natural product Hs Positive 6.5 pIC50 46
⤷ pIC50 6.5 [46]
compound 2 [PMID: 21105727] Small molecule or natural product Click here for species-specific activity table Hs Negative 6.1 pIC50 49
⤷ pIC50 6.1 (IC50 8x10-7 M) [49]
compound 4 [PMID: 21105727] Small molecule or natural product Click here for species-specific activity table Hs Negative 6.0 pIC50 49
⤷ pIC50 6.0 (IC50 1x10-6 M) [49]
compound 3 [PMID: 21105727] Small molecule or natural product Click here for species-specific activity table Hs Negative 5.8 pIC50 49
⤷ pIC50 5.8 (IC50 1.5x10-6 M) [49]
4-MPPTS Small molecule or natural product Hs Positive 5.8 pIC50 2,25-26,48
⤷ pIC50 5.8 [2,25-26,48]
View species-specific allosteric modulator tables
Allosteric Modulator Comments
These positive allosteric modulators appear to act as potentiators of ortheosteric agonist response. These compounds bind within the 7 transmembrane domain of the mGlu2 receptor, have no appreciable response alone, but will increase the affinity of glutamate and DCG-IV [25,48]. These potentiators represent the best selective pharmacological agent for mGlu2 vs. the homologous mGlu3 receptor.

MNI compounds are not selective for mGlu2 over mGlu3; selectivity of compounds for mGlu2 versus other mGlus in references [13,56] and [17] not reported.

CyPPTs and 4APPES are reported to be selective for mGlu2 versus mGlu1,3,4,5,6,7 and 8 [26]. THIIC is also selective for mGlu2 and exhibits allosteric agonist activity in GTPγS binding assays [20]. JNJ-42153065 exhibits allosteric agonist activity with a potency of 270 nM and is reported as >100 fold selective for mGlu2 versus the other mGlus and >50 fold selective for mGlu2 versus other targets in a CEREP panel.

Agonism EC50 of 34 is 4.9 µM, selectivity over other mGlus not reported [7]. Compounds 2,3 and 4 from reference [49] are also mGlu3 PAMs. Compound 14 is reported as selective for mGlu2 among the mGlus [14].

JNJ-40068782 exhibits allosteric agonist activity in certain assays with a potency of 618-925 nM. This activity is seen at the human but not the rat receptor. Also reported to selective for mGlu2 up to 10 µM [31].

Pending publication of data, the value for AZD8529 is derived from the compound record in AstaZeneca's Open Innovation Pharmacology Toolbox.
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Adenylyl cyclase inhibition
Potassium channel
References:  18,21
Tissue Distribution Click here for help
Distribution within the human brain is largely similar to that seen in rodents. Specifically, mGlu2 receptor is localized in layer II and III of the frontal, visual and sensorimotor cortex, several limbic areas including the entorhinal cortex, hippocampus, and amygdala. Also localized within the basal ganglia including caudate, putamen and globus pallidus. Multiple regions of the thalamus, and the granular cell layer of the cerebellum.
Species:  Human
Technique:  immunocytochemistry.
References:  44
CNS: accessory olfactory bulb, neocortex, entorhinal cortex, bed nucleus of the accessory olfactory tract, retrosplenial cortex, hippocampal mossy fibres, molecular layer of the dentate gyrus, basolateral amygdala, striatum, nucleus accumbens, anterior thalamic nuclei, reticular thalamic nucleus, anterior and ventral tegmental nucleus, cerebellar cortex > main olfactory bulb, nucleus of the lateral olfactory tract, perirhinal cortex, central amygdaloid nucleus, triangular septal nucleus, medial habenular nucleus, centromedial thalamic nucleus, rhomboid thalamic nucleus, nucleus reunions of the thalamus, lateroposterior and laterodorsal nuclei of the thalamus, medial mammillary nucleus, interpeduncular nucleus, eriaqueductal gray, ontine nuclei, cochlear nuclei, inferior olivary nucleus, lateral reticular nucleus > olfactory tubercle, piriform cortex, lateral septal nucleus, globus pallidus, principal sensory trigeminal nucleus, lateral preoptic area, ventral pallidum, subthalamic nucleus, substantia nigra, ventral thalamic nuclei, lateral hypothalamic area, ventro- and dorso-medial hypothalamaic nuclei, superior colliculus, ventral tegmental area, vestibular nuclei, nucleus of the solitary tract.
Species:  Mouse
Technique:  immunocytochemistry.
References:  52
Within the brain, mGlu2 receptor is localized both pre- and in some case postsynaptically. Relative distribution is high in several limbic areas including the cortex, hippocampus, amygdala. Also localized within the caudate-putamen and nucleus accumbens of the basal ganglia, rostal portion of the thalamic reticular nucleus, granular cell layer of the cerebellum, and the tegmental nucleus of the lower brain stem.
Species:  Mouse
Technique:  immunocytochemistry.
References:  41
Retina.
Species:  Rat
Technique:  in situ hybridisation.
References:  22
Golgi cells in the cerebellar cortex.
Species:  Rat
Technique:  immunocytochemistry.
References:  33
CNS: accessory olfactory bulb, neocortex, entorhinal cortex, cerebellar cortex > bed nucleus of the accessory olfactory tract, retrosplenial cortex, cingulate cortex, dentate gyrus, triangular septal nucleus, basolateral amygdala, midline thalamic nuclei, anterior thalamic nuclei, medial mammillary nucleus > main olfactory bulb, nucleus of the lateral olfactory tract, piriform cortex, medial septal nucleus, striatum, nucleus accumbens, ventral pallidum, globus pallidus, medial habenular nucleus, pontine nuclei, trapezoid body nucleus, inferior olivary nuclei.
Species:  Rat
Technique:  in situ hybridisation.
References:  42
Within the brain, mGlu2 receptor is localized both pre- and in some case postsynaptically. Relative distribution is high in several limbic areas including the cortex, hippocampus, amygdala. Also localized within the caudate-putamen and nucleus accumbens of the basal ganglia, rostal portion of the thalamic reticular nucleus, granular cell layer of the cerebellum, and the tegmental nucleus of the lower brain stem.
Species:  Rat
Technique:  immunocytochemistry.
References:  41
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Native mGlu2 receptor function has been linked to the regulation of glutamate release with the stimulation of the medial perforant path in hippocampal brain slices.
Species:  Rat
Tissue:  Hippocampal brain slices.
Response measured:  Field Excitatory Postsynaptic Potential with stimulation of the medial periforant pathway.
References:  15,35
Measurement of cAMP levels in CHO cells transfected with the rat mGlu2 receptor.
Species:  Rat
Tissue:  CHO cells.
Response measured:  Inhibition of cAMP production.
References:  53
Measurement of cAMP levels in rat glutamate transporter (RGT) cells transfected with the human mGlu2.
Species:  Human
Tissue:  RGT cells.
Response measured:  Inhibition of cAMP production.
References:  28
Measurement of IP levels in HEK 293 cells transfected with the rat mGlu2 receptor and Gqi9.
Species:  Rat
Tissue:  HEK 293 cells.
Response measured:  IP accumulation.
References:  6
Physiological Functions Click here for help
The mGlu2 receptor is thought to be the major presynaptic autoreceptor, regulating glutamate release.
Species:  Mouse
Tissue:  Hippocampal slices.
References:  27
mGlu2 activation modulates glutamate release in the subthalamic nucleus-globus palidus synapse.
Species:  Rat
Tissue:  Globus pallidus slices.
References:  47
Physiological Consequences of Altering Gene Expression Click here for help
Loss of mGlu2/3 agonist suppression of glutamate release and hippocampal mossy fiber long-term depression in mGlu2 knock-out mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  55
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Grm2tm1Ddsc Grm2tm1Ddsc/Grm2tm1Ddsc
involves: 129S1/Sv * 129X1/SvJ * CD-1		 MGI:1351339  MP:0001362 abnormal anxiety-related response PMID: 15619115 
Grm2tm1Nak Grm2tm1Nak/Grm2tm1Nak
involves: 129S/SvEv		 MGI:1351339  MP:0002912 abnormal excitatory postsynaptic potential PMID: 8662555 
Grm2tm1Nak Grm2tm1Nak/Grm2tm1Nak
B6.129S-Grm2		 MGI:1351339  MP:0002066 abnormal motor capabilities/coordination/movement PMID: 15753323 
Grm2tm1Nak Grm2tm1Nak/Grm2tm1Nak
B6.129S-Grm2		 MGI:1351339  MP:0001988 cocaine preference PMID: 15753323 
Grm2tm1Nak Grm2tm1Nak/Grm2tm1Nak
B6.129S-Grm2		 MGI:1351339  MP:0001399 hyperactivity PMID: 15753323 
Grm2tm1Nak Grm2tm1Nak/Grm2tm1Nak
B6.129S-Grm2		 MGI:1351339  MP:0001405 impaired coordination PMID: 15753323 
Grm2tm1Nak Grm2tm1Nak/Grm2tm1Nak
B6.129S-Grm2		 MGI:1351339  MP:0001906 increased dopamine level PMID: 15753323 
Grm2tm1Nak Grm2tm1Nak/Grm2tm1Nak
involves: 129S/SvEv		 MGI:1351339  MP:0001475 reduced long term depression PMID: 8662555 
General Comments
To date, the relative lack of mGlu2 vs. mGlu3 receptor agonists/antagonists and limited results/availability of with selective antibodies has hampered efforts to differentiate the relative roles of these two highly related receptors in the Group II mGlu receptor family.

References

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1. AstraZeneca. AZD8529-Open Innovation. Accessed on 10/09/2014. Modified on 10/09/2014. astrazeneca.com, http://openinnovation.astrazeneca.com/what-we-offer/compound/azd8529/

2. Barda DA, Wang ZQ, Britton TC, Henry SS, Jagdmann GE, Coleman DS, Johnson MP, Andis SL, Schoepp DD. (2004) SAR study of a subtype selective allosteric potentiator of metabotropic glutamate 2 receptor, N-(4-phenoxyphenyl)-N-(3-pyridinylmethyl)ethanesulfonamide. Bioorg Med Chem Lett, 14 (12): 3099-102. [PMID:15149652]

3. Bertrand HO, Bessis AS, Pin JP, Acher FC. (2002) Common and selective molecular determinants involved in metabotopic glutamate receptor agonist activity. J Med Chem, 45 (15): 3171-83. [PMID:12109902]

4. Bonnefous C, Vernier JM, Hutchinson JH, Gardner MF, Cramer M, James JK, Rowe BA, Daggett LP, Schaffhauser H, Kamenecka TM. (2005) Biphenyl-indanones: allosteric potentiators of the metabotropic glutamate subtype 2 receptor. Bioorg Med Chem Lett, 15 (19): 4354-8. [PMID:16046122]

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