mGlu2 receptor

Target id: 290

Nomenclature: mGlu2 receptor

Family: Metabotropic glutamate receptors

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for mGlu2 receptor in GtoImmuPdb

Gene and Protein Information
class C G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 872 3q21.31 GRM2 glutamate metabotropic receptor 2 21,36
Mouse 7 872 9 Grm2 glutamate receptor, metabotropic 2
Rat 7 872 8q32 Grm2 glutamate metabotropic receptor 2 52
Previous and Unofficial Names
mGluR2
GPRC1B
metabotropic glutamate receptor 2
glutamate receptor
Database Links
Specialist databases
GPCRDB grm2_human (Hs), grm2_mouse (Mm), grm2_rat (Rn)
Other databases
ChEMBL Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
L-glutamic acid
Comments: Other endogenous ligands include L-aspartic acid, L-serine-O-phosphate, NAAG and L-cysteine sulphinic acid

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]eglumegad Rn Full agonist 7.7 pKd 50
pKd 7.7 [50]
MGS0028 Rn Full agonist 9.2 pKi 38
pKi 9.2 [38]
LY379268 Hs Full agonist 7.9 pKi 37
pKi 7.9 [37]
eglumegad Rn Full agonist 7.8 – 7.9 pKi 9,50
pKi 7.8 – 7.9 [9,50]
DCG-IV Rn Full agonist 7.0 pKi 9,50
pKi 7.0 [9,50]
L-CCG-I Rn Full agonist 6.8 – 7.0 pKi 9,50
pKi 6.8 – 7.0 [9,50]
eglumegad Hs Full agonist 6.9 pKi 24
pKi 6.9 [24]
DCG-IV Hs Full agonist 6.5 pKi 24
pKi 6.5 [24]
L-CCG-I Hs Full agonist 6.3 pKi 24
pKi 6.3 [24]
L-glutamic acid Rn Full agonist 5.4 – 5.9 pKi 5,19
pKi 5.4 – 5.9 [5,19]
(1S,3R)-ACPD Rn Full agonist 5.0 – 5.4 pKi 9,50
pKi 5.0 – 5.4 [9,50]
(2R,3R)-APDC Hs Full agonist 5.0 pKi 24
pKi 5.0 [24]
L-glutamic acid Hs Full agonist 4.9 pKi 24
pKi 4.9 [24]
(S)-4C3HPG Rn Full agonist 4.8 pKi 9
pKi 4.8 [9]
(1S,3R)-ACPD Hs Full agonist 4.2 pKi 24
pKi 4.2 [24]
L-glutamic acid Hs Agonist 4.7 – 5.4 pEC50 44
pEC50 4.7 – 5.4 [44]
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 [49]. 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 [3,35].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]LY341495 Hs Antagonist 8.8 pKd 24
pKd 8.8 [24]
MGS0039 Rn Antagonist 8.6 – 8.7 pKi 10,39
pKi 8.6 – 8.7 [10,39]
LY341495 Hs Antagonist 8.6 pKi 24
pKi 8.6 [24]
LY341495 Rn Antagonist 7.7 – 9.0 pKi 9,50
pKi 7.7 – 9.0 [9,50]
α-methylserine-O-phosphate Rn Antagonist 5.3 pKi 9
pKi 5.3 [9]
(+)-MCPG Rn Antagonist 4.6 pKi 9
pKi 4.6 [9]
eGlu Rn Antagonist 4.4 – 4.6 pKi 9,50
pKi 4.4 – 4.6 [9,50]
(+)-MCPG Hs Antagonist 3.8 pKi 24
pKi 3.8 [24]
PCCG-4 Rn Antagonist 5.1 pIC50 42
pIC50 5.1 (IC50 8x10-6 M) [42]
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 [49]. 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 Affinity Units Reference
JNJ-46281222 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 Rn Positive 8.4 pKd 33
pKd 8.4 (Kd 4.2x10-9 M) [33]
[3H]JNJ-40068782 Rn Positive 8.0 pKd 31
pKd 8.0 (Kd 1x10-8 M) [31]
[3H]JNJ-40068782 Hs Positive 7.9 pKd 31
pKd 7.9 (Kd 1.2x10-8 M) [31]
RO4988546 Rn Negative 8.6 pKi 33
pKi 8.6 (Ki 2.3x10-9 M) [33]
RO5488608 Rn Negative 7.9 – 8.7 pKi 33
pKi 7.9 – 8.7 (Ki 1.14x10-8 – 1.9x10-9 M) [33]
JNJ-46281222 Hs Positive 8.3 pKi 16
pKi 8.3 (Ki 4.68x10-9 M) [16]
Description: Homologous displacement assay.
Ro4491533 Rn Negative 8.3 pKi 8
pKi 8.3 (Ki 5.4x10-9 M) [8]
JNJ-42153605 Hs Positive 7.8 pKi 12
pKi 7.8 (Ki 1.5x10-8 M) [12]
Ro4491533 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] Hs Negative 6.2 pKi 48
pKi 6.2 (Ki 6x10-7 M) [48]
compound 4 [PMID: 21105727] Hs Negative 6.1 pKi 48
pKi 6.1 (Ki 8x10-7 M) [48]
compound 2 [PMID: 21105727] Hs Negative 6.0 pKi 48
pKi 6.0 (Ki 1x10-6 M) [48]
THIIC Rn Positive 7.9 pEC50 20
pEC50 7.9 (EC50 1.28x10-8 M) [20]
2,2,2-TEMPS Hs Positive 7.8 pEC50 2
pEC50 7.8 (EC50 1.4x10-8 M) [2]
JNJ-42153605 Hs Positive 7.8 pEC50 12
pEC50 7.8 (EC50 1.7x10-8 M) [12]
THIIC Hs Positive 7.7 pEC50 20
pEC50 7.7 (EC50 2.25x10-8 M) [20]
compound 14a [PMID: 18812259] Rn Positive 7.6 pEC50 55
pEC50 7.6 (EC50 2.6x10-8 M) [55]
cyPPTS Hs Positive 7.6 pEC50 26
pEC50 7.6 (EC50 2.4x10-8 M) [26]
compound 14c [PMID: 18812259] Rn Positive 7.5 pEC50 55
pEC50 7.5 (EC50 3x10-8 M) [55]
JNJ-40068782 Hs Positive 6.8 – 7.8 pEC50 31
pEC50 6.8 – 7.8 (EC50 1.43x10-7 – 1.5x10-8 M) [31]
JNJ-40068782 Rn Positive 7.3 pEC50 31
pEC50 7.3 (EC50 5.2x10-8 M) [31]
compound 19 [PMID: 18812259] Rn Positive 7.2 pEC50 55
pEC50 7.2 (EC50 6.4x10-8 M) [55]
GSK1331258 Hs Positive 7.1 pEC50 13
pEC50 7.1 (EC50 8x10-8 M) [13]
compound 34 [PMID: 20409708] Hs Positive 7.1 pEC50 7
pEC50 7.1 (EC50 8.4x10-8 M) [7]
CBiPES Hs Positive 7.0 pEC50 26
pEC50 7.0 (EC50 9.28x10-8 M) [26]
biphenylindanone A Hs Positive 7.0 pEC50 4
pEC50 7.0 (EC50 1.11x10-7 M) [4]
GSK1331268 Hs Positive 6.9 pEC50 13
pEC50 6.9 (EC50 1.25x10-7 M) [13]
JNJ-40411813 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] Rn Positive 6.8 pEC50 14
pEC50 6.8 (EC50 1.7x10-7 M) [14]
AZD8529 Hs Positive 6.7 pEC50 1
pEC50 6.7 (EC50 1.95x10-7 M) [1]
compound 48 [PMID: 22364337] Hs Positive 6.4 pEC50 11
pEC50 6.4 (EC50 3.61x10-7 M) [11]
4-APPES Hs Positive 5.7 pEC50 26
pEC50 5.7 (EC50 2.26x10-6 M) [26]
RO4988546 Rn Negative 8.3 pIC50 33
pIC50 8.3 (IC50 5.5x10-9 M) [33]
MNI-137 Rn Negative 7.7 – 8.1 pIC50 23
pIC50 7.7 – 8.1 (IC50 2.03x10-8 – 8.3x10-9 M) [23]
Ro4491533 Hs Negative 7.8 pIC50 53
pIC50 7.8 (IC50 1.4x10-8 M) [53]
MNI-136 Hs Negative 7.3 – 8.1 pIC50 23
pIC50 7.3 – 8.1 (IC50 4.66x10-8 – 8.8x10-9 M) [23]
MNI-136 Rn Negative 7.7 – 7.7 pIC50 23
pIC50 7.7 – 7.7 (IC50 2.13x10-8 – 1.97x10-8 M) [23]
MNI-135 Rn Negative 7.5 – 7.7 pIC50 23
pIC50 7.5 – 7.7 (IC50 3.02x10-8 – 1.96x10-8 M) [23]
Ro4491533 Rn Negative 6.5 – 8.7 pIC50 8,53
pIC50 6.5 – 8.7 (IC50 2.96x10-7 – 2x10-9 M) [8,53]
MNI-137 Hs Negative 7.1 – 7.9 pIC50 23
pIC50 7.1 – 7.9 (IC50 7.27x10-8 – 1.26x10-8 M) [23]
MNI-135 Hs Negative 6.9 – 8.0 pIC50 23
pIC50 6.9 – 8.0 (IC50 1.18x10-7 – 1.05x10-8 M) [23]
Ro64-5229 Rn Negative 7.0 pIC50 29
pIC50 7.0 (IC50 1.1x10-7 M) [29]
3-MPPTS Hs Positive 6.6 pIC50 25-26,47
pIC50 6.6 [25-26,47]
PTBE Hs Positive 6.5 pIC50 45
pIC50 6.5 [45]
compound 2 [PMID: 21105727] Hs Negative 6.1 pIC50 48
pIC50 6.1 (IC50 8x10-7 M) [48]
compound 4 [PMID: 21105727] Hs Negative 6.0 pIC50 48
pIC50 6.0 (IC50 1x10-6 M) [48]
compound 3 [PMID: 21105727] Hs Negative 5.8 pIC50 48
pIC50 5.8 (IC50 1.5x10-6 M) [48]
4-MPPTS Hs Positive 5.8 pIC50 2,25-26,47
pIC50 5.8 [2,25-26,47]
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 [25,47]. 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 [13,55] 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 [48] 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
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
Potassium channel
References:  18,21
Tissue Distribution
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:  43
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:  51
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:  40
Retina.
Species:  Rat
Technique:  in situ hybridisation.
References:  22
Golgi cells in the cerebellar cortex.
Species:  Rat
Technique:  immunocytochemistry.
References:  32
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:  41
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:  40
Expression Datasets

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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
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:  15,34
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:  52
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
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:  46
Physiological Consequences of Altering Gene Expression
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:  54
Phenotypes, Alleles and Disease Models 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: 3099- 3102. [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: 3171- 3183. [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]

5. Boss V, Nutt KM, Conn PJ. (1994) L-cysteine sulfinic acid as an endogenous agonist of a novel metabotropic receptor coupled to stimulation of phospholipase D activity. Mol Pharmacol.45: 1177-1182. [PMID:8022410]

6. Brabet I, Parmentier ML, de Colle C, Bockaert J, Acher F, Pin JP. (1998) Comparative effect of L-CCG-I, DCG-IV and gamma-carboxy-L-glutamate on all cloned metabotropic glutamate receptor subtypes. Neuropharmacology.37: 1043-1051. [PMID:9833633]

7. Brnardic EJ, Fraley ME, Garbaccio RM, Layton ME, Sanders JM, Culberson C, Jacobson MA, Magliaro BC, Hutson PH, O'Brien JA et al.. (2010) 3-Aryl-5-phenoxymethyl-1,3-oxazolidin-2-ones as positive allosteric modulators of mGluR2 for the treatment of schizophrenia: Hit-to-lead efforts. Bioorg. Med. Chem. Lett.20 (10): 3129-33. [PMID:20409708]

8. Campo B, Kalinichev M, Lambeng N, El Yacoubi M, Royer-Urios I, Schneider M, Legrand C, Parron D, Girard F, Bessif A et al.. (2011) Characterization of an mGluR2/3 negative allosteric modulator in rodent models of depression. J. Neurogenet.25 (4): 152-66. [PMID:22091727]

9. Cartmell J, Adam G, Chaboz S, Henningsen R, Kemp JA, Klingelschmidt A, Metzler V, Monsma F, Schaffhauser H, Wichmann J, Mutel V. (1998) Characterization of [3H]-(2S,2'R,3'R)-2-(2',3'-dicarboxy-cyclopropyl)glycine ([3H]-DCG IV) binding to metabotropic mGlu2 receptor-transfected cell membranes. Br J Pharmacol.123: 497- 504. [PMID:9504391]

10. Chaki S, Yoshikawa R, Hirota S, Shimazaki T, Maeda M, Kawashima N, Yoshimizu T, Yasuhara A, Sakagami K, Okuyama S, Nakanishi S, Nakazato A. (2004) MGS0039: a potent and selective group II metabotropic glutamate receptor antagonist with antidepressant-like activity. Neuropharmacology46: 457-467. [PMID:14975669]

11. Cid JM, Duvey G, Tresadern G, Nhem V, Furnari R, Cluzeau P, Vega JA, de Lucas AI, Matesanz E, Alonso JM et al.. (2012) Discovery of 1,4-disubstituted 3-cyano-2-pyridones: a new class of positive allosteric modulators of the metabotropic glutamate 2 receptor. J. Med. Chem.55 (5): 2388-405. [PMID:22364337]

12. Cid JM, Tresadern G, Vega JA, de Lucas AI, Matesanz E, Iturrino L, Linares ML, Garcia A, Andrés JI, Macdonald GJ et al.. (2012) Discovery of 3-cyclopropylmethyl-7-(4-phenylpiperidin-1-yl)-8-trifluoromethyl[1,2,4]triazolo[4,3-a]pyridine (JNJ-42153605): a positive allosteric modulator of the metabotropic glutamate 2 receptor. J. Med. Chem.55 (20): 8770-89. [PMID:23072213]

13. D'Alessandro PL, Corti C, Roth A, Ugolini A, Sava A, Montanari D, Bianchi F, Garland SL, Powney B, Koppe EL et al.. (2010) The identification of structurally novel, selective, orally bioavailable positive modulators of mGluR2. Bioorg. Med. Chem. Lett.20 (2): 759-62. [PMID:20005096]

14. Dhanya RP, Sidique S, Sheffler DJ, Nickols HH, Herath A, Yang L, Dahl R, Ardecky R, Semenova S, Markou A et al.. (2011) Design and synthesis of an orally active metabotropic glutamate receptor subtype-2 (mGluR2) positive allosteric modulator (PAM) that decreases cocaine self-administration in rats. J. Med. Chem.54 (1): 342-53. [PMID:21155570]

15. Dietrich D, Beck H, Kral T, Clusmann H, Elger CE, Schramm J. (1997) Metabotropic glutamate receptors modulate synaptic transmission in the perforant path: pharmacology and localization of two distinct receptors. Brain Res.767: 220- 227. [PMID:9367251]

16. Doornbos ML, Pérez-Benito L, Tresadern G, Mulder-Krieger T, Biesmans I, Trabanco AA, Cid JM, Lavreysen H, IJzerman AP, Heitman LH. (2015) Molecular mechanism of positive allosteric modulation of the metabotropic glutamate receptor 2 by JNJ-46281222. Br. J. Pharmacol.,  [Epub ahead of print]. [PMID:26589404]

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Francine Acher, P. Jeffrey Conn, Robert Duvoisin, Francesco Ferraguti, Peter J. Flor, David Hampson, Michael P. Johnson, James Monn, Shigetada Nakanishi, Ferdinando Nicoletti, Jean-Philippe Pin, Darryle D. Schoepp, Ryuichi Shigemoto.
Metabotropic glutamate receptors: mGlu2 receptor. Last modified on 06/03/2017. Accessed on 29/06/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=290.