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mGlu5 receptor

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Target not currently curated in GtoImmuPdb

Target id: 293

Nomenclature: mGlu5 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 1212 11q14.2-q14.3 GRM5 glutamate metabotropic receptor 5 60-61
Mouse 7 1203 7 D3 Grm5 glutamate receptor, metabotropic 5
Rat 7 1203 1q32 Grm5 glutamate metabotropic receptor 5 1,41
Previous and Unofficial Names Click here for help
mGluR5 | GPRC1E | glutamate receptor
Database Links Click here for help
Specialist databases
GPCRdb grm5_human (Hs), grm5_mouse (Mm), grm5_rat (Rn)
Other databases
Alphafold P41594 (Hs), Q3UVX5 (Mm), P31424 (Rn)
ChEMBL Target CHEMBL3227 (Hs), CHEMBL1641352 (Mm), CHEMBL2564 (Rn)
DrugBank Target P41594 (Hs)
Ensembl Gene ENSG00000168959 (Hs), ENSMUSG00000049583 (Mm), ENSRNOG00000016429 (Rn)
Entrez Gene 2915 (Hs), 108071 (Mm), 24418 (Rn)
Human Protein Atlas ENSG00000168959 (Hs)
KEGG Gene hsa:2915 (Hs), mmu:108071 (Mm), rno:24418 (Rn)
OMIM 604102 (Hs)
Pharos P41594 (Hs)
RefSeq Nucleotide NM_000842 (Hs), NM_001143831 (Hs), NM_001081414 (Mm), NM_017012 (Rn)
RefSeq Protein NP_001137303 (Hs), NP_000833 (Hs), NP_001074883 (Mm), NP_058708 (Rn)
UniProtKB P41594 (Hs), Q3UVX5 (Mm), P31424 (Rn)
Wikipedia GRM5 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the human class C GPCR metabotropic glutamate receptor 5 transmembrane domain in complex with the negative allosteric modulator mavoglurant
PDB Id:  4OO9
Ligand:  mavoglurant
Resolution:  2.6Å
Species:  Human
References:  23
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

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
VU0424465 Small molecule or natural product Rn Agonist 6.8 pEC50 82
⤷ pEC50 6.8 (EC50 1.71x10-7 M) [82]
VU0092273 Small molecule or natural product Rn Agonist 5.9 pEC50 65
⤷ pEC50 5.9 (EC50 1.3x10-6 M) [65]
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 5.0 – 5.5 pEC50 72
⤷ pEC50 5.0 – 5.5 [72]
(S)-(+)-CBPG Small molecule or natural product Click here for species-specific activity table Rn Partial agonist 4.3 pEC50 56
⤷ pEC50 4.3 (EC50 4.7x10-5 M) [56]
quisqualate Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Full agonist 7.5 pIC50 63
⤷ pIC50 7.5 [63]
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 6.1 pIC50 63
⤷ pIC50 6.1 [63]
L-CCG-I Small molecule or natural product Click here for species-specific activity table Rn Full agonist 5.8 pIC50 63
⤷ pIC50 5.8 [63]
(1S,3R)-ACPD Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Full agonist 5.7 pIC50 63
⤷ pIC50 5.7 [63]
ibotenic acid Small molecule or natural product Click here for species-specific activity table Rn Full agonist 5.7 pIC50 63
⤷ pIC50 5.7 [63]
3,5-DHPG Small molecule or natural product Click here for species-specific activity table Rn Partial agonist 5.4 pIC50 63
⤷ pIC50 5.4 [63]
(S)-3HPG Small molecule or natural product Click here for species-specific activity table Rn Partial agonist 5.0 pIC50 63
⤷ pIC50 5.0 [63]
CHPG Small molecule or natural product Hs Full agonist 3.4 pIC50 63
⤷ pIC50 3.4 [63]
View species-specific agonist tables
Agonist Comments
Indicated affinities were determined by displacement studies of [3H]quisqualate bound on HEK cell membranes expressing a recombinant rat mGlu5. This is the only study describing affinity values for these compounds. More information on agonist potencies determined from functional studies can be obtained from [85]. So far no differences have been reported for the agonist affinities between the rat and the human receptor.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[11C]JNJ-16567083 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Rn Antagonist 5.6 pKi 38
⤷ pKi 5.6 (Ki 2.366x10-6 M) [38]
methoxy-MPEP Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Antagonist 8.4 pIC50 29
⤷ pIC50 8.4 (IC50 3.6x10-9 M) [29]
Description: [3H]-M-MPEP displacement assay.
ACDPP Small molecule or natural product Hs Antagonist 6.9 pIC50 6
⤷ pIC50 6.9 [6]
(S)-4C3HPG Small molecule or natural product Click here for species-specific activity table Rn Antagonist 5.6 pIC50 63
⤷ pIC50 5.6 [63]
LY341495 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 5.1 pIC50 44
⤷ pIC50 5.1 [44]
DCG-IV Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 4.7 pIC50 63
⤷ pIC50 4.7 [63]
(S)-4CPG Small molecule or natural product Click here for species-specific activity table Rn Antagonist 4.6 pIC50 63
⤷ pIC50 4.6 [63]
(+)-MCPG Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 3.7 pIC50 63
⤷ pIC50 3.7 [63]
View species-specific antagonist tables
Antagonist Comments
Indicated affinities were determined by displacement studies of [3H]quisqualate bound on HEK cell membranes expressing a recombinant rat mGlu5 (except for LY341495 value determined from functional studies). This is the only study describing affinity values for these compounds.

More information on agonist potencies determined from functional studies can be obtained from [85]. So far no differences have been reported for the antagonist affinities between the rat and the human receptor.

Surprisingly, although LY367385 and AIDA displace Quisqualate binding, no antagonistic activity of these compounds have been observed in functional studies (see [85]). (S)-4C3HPG has been reported to have slight partial agonist activity at this receptor [41].
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
VU0409551 Small molecule or natural product Hs Positive 7.1 pKB 83
⤷ pKB 7.1 [83]
VU0360172 Small molecule or natural product Hs Positive 6.6 – 7.0 pKB 32,77
⤷ pKB 6.6 – 7.0 [32,77]
VU0483605 Small molecule or natural product Rn Positive 6.5 pKB 36
⤷ pKB 6.5 [36]
GS39783 Small molecule or natural product Ligand has a PDB structure Rn Neutral 6.3 pKB 36
⤷ pKB 6.3 [36]
PHCCC Small molecule or natural product Click here for species-specific activity table Rn Neutral 5.6 pKB 36
⤷ pKB 5.6 [36]
AZ12216052 Small molecule or natural product Rn Positive 5.4 pKB 36
⤷ pKB 5.4 [36]
NPS 2143 Small molecule or natural product Ligand has a PDB structure Rn Positive 5.1 pKB 36
⤷ pKB 5.1 [36]
CPCCOEt Small molecule or natural product Click here for species-specific activity table Rn Neutral 4.9 pKB 36
⤷ pKB 4.9 [36]
CGP7930 Small molecule or natural product Click here for species-specific activity table Rn Positive 4.8 pKB 36
⤷ pKB 4.8 [36]
[3H]CTEP Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Negative 8.8 pKd 48
⤷ pKd 8.8 (Kd 1.5x10-9 M) [48]
[3H]CTEP Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Negative 8.8 pKd 48
⤷ pKd 8.8 (Kd 1.7x10-9 M) [48]
[3H]CTEP Small molecule or natural product Ligand is labelled Ligand is radioactive Mm Negative 8.7 pKd 48
⤷ pKd 8.7 (Kd 1.8x10-9 M) [48]
[3H]methoxy-PEPy Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Negative 8.5 pKd 20
⤷ pKd 8.5 (Kd 3.4x10-9 M) [20]
[3H]methoxymethyl-MTEP Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Negative 7.7 pKd 20
⤷ pKd 7.7 (Kd 2x10-8 M) [20]
[3H]fenobam Small molecule or natural product Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Negative 7.5 pKd 75
⤷ pKd 7.5 [75]
[3H]fenobam Small molecule or natural product Ligand is labelled Ligand is radioactive Ligand has a PDB structure Rn Negative 7.3 pKd 75
⤷ pKd 7.3 [75]
compound 20 [PMID: 16439120] Small molecule or natural product Rn Negative 9.0 pKi 13
⤷ pKi 9.0 (Ki 1x10-9 M) [13]
BOMA Small molecule or natural product Hs Negative 8.5 pKi 101
⤷ pKi 8.5 [101]
AZD9272 Small molecule or natural product Hs Negative 8.4 pKi 76
⤷ pKi 8.4 (Ki 3.8x10-9 M) [76]
GRN-529 Small molecule or natural product Rn Negative 8.3 pKi 39
⤷ pKi 8.3 (Ki 5.4x10-9 M) [39]
CTEP Small molecule or natural product Mm Negative 8.0 pKi 48
⤷ pKi 8.0 (Ki 9.5x10-9 M) [48]
compound 26 [PMID: 16439120] Small molecule or natural product Rn Negative 8.0 pKi 13
⤷ pKi 8.0 (Ki 1x10-8 M) [13]
compound 30 [PMID: 21757343] Small molecule or natural product Hs Negative 7.9 pKi 102
⤷ pKi 7.9 (Ki 1.2x10-8 M) [102]
compound 10 [PMID: 15482906] Small molecule or natural product Hs Negative 7.9 pKi 37
⤷ pKi 7.9 (Ki 1.2x10-8 M) [37]
CTEP Small molecule or natural product Rn Negative 7.9 pKi 48
⤷ pKi 7.9 (Ki 1.26x10-8 M) [48]
compound 8 [PMID: 15482908] Small molecule or natural product Rn Negative 7.8 pKi 91
⤷ pKi 7.8 (Ki 1.4x10-8 M) [91]
MTEP Small molecule or natural product Hs Negative 7.8 pKi 10
⤷ pKi 7.8 (Ki 1.6x10-8 M) [10]
VU0285683 Small molecule or natural product Rn Negative 7.8 pKi 77
⤷ pKi 7.8 (Ki 1.6x10-8 M) [77]
compound 29b [PMID: 20809633] Small molecule or natural product Rn Negative 7.8 pKi 12
⤷ pKi 7.8 (Ki 1.7x10-8 M) [12]
CTEP Small molecule or natural product Hs Negative 7.7 – 7.8 pKi 40,48
⤷ pKi 7.7 – 7.8 (Ki 2x10-8 – 1.64x10-8 M) [40,48]
compound 10 [PMID: 15482908] Small molecule or natural product Rn Negative 7.7 pKi 91
⤷ pKi 7.7 (Ki 1.9x10-8 M) [91]
compound 23 [PMID: 17590335] Small molecule or natural product Rn Negative 7.7 pKi 58
⤷ pKi 7.7 (Ki 2.2x10-8 M) [58]
AZD6538 Small molecule or natural product Hs Negative 7.6 pKi 76
⤷ pKi 7.6 (Ki 2.8x10-8 M) [76]
compound 24d [PMID: 23357634] Small molecule or natural product Rn Negative 7.5 pKi 108
⤷ pKi 7.5 (Ki 3x10-8 M) [108]
basimglurant Small molecule or natural product Hs Negative 7.4 pKi 40
⤷ pKi 7.4 (Ki 3.6x10-8 M) [40]
Description: Reduction of antagonist MPEP binding to mGlu5 receptors in vitro
compound 16m [PMID: 19931453] Small molecule or natural product Hs Negative 7.4 pKi 92
⤷ pKi 7.4 (Ki 3.8x10-8 M) [92]
VU0366058 Small molecule or natural product Rn Negative 7.1 pKi 62
⤷ pKi 7.1 (Ki 8.4x10-8 M) [62]
compound 16a [PMID: 14697765] Small molecule or natural product Rn Negative 7.0 pKi 101
⤷ pKi 7.0 (Ki 9.1x10-8 M) [101]
compound 42 [PMID: 17189691] Small molecule or natural product Rn Negative 7.0 pKi 14
⤷ pKi 7.0 (Ki 9.5x10-8 M) [14]
compound 8 [PMID: 20598884] Small molecule or natural product Rn Negative 7.0 pKi 25
⤷ pKi 7.0 (Ki 1.02x10-7 M) [25]
VU-1545 Small molecule or natural product Rn Positive 6.8 pKi 22
⤷ pKi 6.8 (Ki 1.56x10-7 M) [22]
compound 11a [PMID: 14697765] Small molecule or natural product Rn Negative 6.8 pKi 101
⤷ pKi 6.8 (Ki 1.59x10-7 M) [101]
VU0360172 Small molecule or natural product Rn Positive 6.7 pKi 77
⤷ pKi 6.7 (Ki 1.95x10-7 M) [77]
compound 27 [PMID: 20598884] Small molecule or natural product Rn Negative 6.7 pKi 25
⤷ pKi 6.7 (Ki 2.06x10-7 M) [25]
VU-29 Small molecule or natural product Rn Positive 6.6 pKi 16
⤷ pKi 6.6 (Ki 2.44x10-7 M) [16]
M-5MPEP Small molecule or natural product Rn Negative 6.5 pKi 78
⤷ pKi 6.5 (Ki 3x10-7 M) [78]
Br-5MPEPy Small molecule or natural product Rn Negative 6.5 pKi 78
⤷ pKi 6.5 (Ki 3x10-7 M) [78]
LSN2463359 Small molecule or natural product Ligand has a PDB structure Rn Positive 6.4 pKi 31
⤷ pKi 6.4 (Ki 3.77x10-7 M) [31]
5-MPEP Small molecule or natural product Rn Neutral 6.4 pKi 78
⤷ pKi 6.4 [78]
compound 18 [PMID: 21927650] Small molecule or natural product Rn Negative 6.3 pKi 49
⤷ pKi 6.3 (Ki 4.77x10-7 M) [49]
LSN2814617 Small molecule or natural product Rn Positive 5.9 pKi 31
⤷ pKi 5.9 (Ki 1.34x10-6 M) [31]
5PAM523 Small molecule or natural product Rn Positive 5.7 pKi 69
⤷ pKi 5.7 (Ki 2x10-6 M) [69]
CPPZ Small molecule or natural product Rn Positive 5.5 pKi 93
⤷ pKi 5.5 (Ki 3.1x10-6 M) [93]
ADX-47273 Small molecule or natural product Rn Positive 5.4 pKi 31
⤷ pKi 5.4 (Ki 3.65x10-6 M) [31]
cinacalcet Small molecule or natural product Approved drug Ligand has a PDB structure Rn Positive 4.3 pKi 36
⤷ pKi 4.3 [36]
VU0424465 Small molecule or natural product Rn Positive 8.8 pEC50 82
⤷ pEC50 8.8 (EC50 1.5x10-9 M) [82]
VU0404251 Small molecule or natural product Rn Positive 8.1 pEC50 55
⤷ pEC50 8.1 (EC50 7.2x10-9 M) [55]
VU-29 Small molecule or natural product Rn Positive 8.1 pEC50 16
⤷ pEC50 8.1 (EC50 9x10-9 M) [16]
VU-1545 Small molecule or natural product Hs Positive 8.0 pEC50 22
⤷ pEC50 8.0 (EC50 9.6x10-9 M) [22]
VU0463841 Small molecule or natural product Rn Negative 7.9 pEC50 2
⤷ pEC50 7.9 (EC50 1.3x10-8 M) [2]
compound 41 [PMID: 23434029] Small molecule or natural product Hs Negative 7.9 pEC50 15
⤷ pEC50 7.9 (EC50 1.3x10-8 M) [15]
CDPPB Small molecule or natural product Ligand has a PDB structure Hs Positive 7.6 – 8.0 pEC50 45,50
⤷ pEC50 7.6 – 8.0 [45,50]
VU0360172 Small molecule or natural product Rn Positive 7.8 pEC50 77
⤷ pEC50 7.8 (EC50 1.6x10-8 M) [77]
CDPPB Small molecule or natural product Ligand has a PDB structure Rn Positive 7.7 pEC50 50
⤷ pEC50 7.7 [50]
LSN2463359 Small molecule or natural product Ligand has a PDB structure Rn Positive 7.6 pEC50 31
⤷ pEC50 7.6 (EC50 2.4x10-8 M) [31]
LSN2463359 Small molecule or natural product Ligand has a PDB structure Hs Positive 7.5 pEC50 31
⤷ pEC50 7.5 (EC50 3.3x10-8 M) [31]
VU0357121 Small molecule or natural product Rn Positive 7.5 pEC50 33
⤷ pEC50 7.5 (EC50 3.3x10-8 M) [33]
VU0092273 Small molecule or natural product Rn Positive 7.5 pEC50 65
⤷ pEC50 7.5 (EC50 3.5x10-8 M) [65]
VU0240382 Small molecule or natural product Rn Positive 7.4 pEC50 65
⤷ pEC50 7.4 (EC50 3.9x10-8 M) [65]
compound 47 [PMID: 21295468] Small molecule or natural product Hs Positive 7.3 pEC50 98
⤷ pEC50 7.3 (EC50 5.01x10-8 M) [98]
LSN2814617 Small molecule or natural product Hs Positive 7.3 pEC50 31
⤷ pEC50 7.3 (EC50 5.2x10-8 M) [31]
ADX-47273 Small molecule or natural product Rn Positive 7.3 pEC50 31
⤷ pEC50 7.3 (EC50 5.5x10-8 M) [31]
VU0404251 Small molecule or natural product Hs Positive 7.2 pEC50 55
⤷ pEC50 7.2 (EC50 7x10-8 M) [55]
LSN2814617 Small molecule or natural product Rn Positive 7.0 pEC50 31
⤷ pEC50 7.0 (EC50 9.3x10-8 M) [31]
VU0361747 Small molecule or natural product Rn Positive 6.9 pEC50 65
⤷ pEC50 6.9 (EC50 1.26x10-7 M) [65]
ADX-47273 Small molecule or natural product Hs Positive 6.8 pEC50 31
⤷ pEC50 6.8 (EC50 1.57x10-7 M) [31]
5PAM523 Small molecule or natural product Hs Positive 6.7 pEC50 69
⤷ pEC50 6.7 (EC50 2.01x10-7 M) [69]
5PAM523 Small molecule or natural product Rn Positive 6.5 pEC50 69
⤷ pEC50 6.5 (EC50 3.11x10-7 M) [69]
NCFP Small molecule or natural product Rn Positive 6.0 – 6.7 pEC50 64
⤷ pEC50 6.7 (EC50 2.14x10-7 M) EC50 with high mGlu5 expression [64]
pEC50 6.4 (EC50 3.7x10-7 M) EC50 with low mGlu5 expression [64]
pEC50 6.0 (EC50 9.69x10-7 M) EC50 from assay using rat astrocytes [64]
CPPZ Small molecule or natural product Hs Positive 6.3 pEC50 93
⤷ pEC50 6.3 (EC50 5x10-7 M) [93]
VU0364289 Small molecule or natural product Rn Positive 5.8 pEC50 109
⤷ pEC50 5.8 (EC50 1.6x10-6 M) [109]
SP203 Small molecule or natural product Rn Negative 10.4 pIC50 89
⤷ pIC50 10.4 (IC50 3.6x10-11 M) [89]
compound 18 [PMID: 17723296] Small molecule or natural product Rn Negative 9.1 pIC50 103
⤷ pIC50 9.1 (IC50 7.2x10-10 M) [103]
compound 23 [PMID: 17590335] Small molecule or natural product Rn Negative 9.1 pIC50 58
⤷ pIC50 9.1 (IC50 8x10-10 M) [58]
MTEB Small molecule or natural product Hs Negative 8.7 pIC50 101
⤷ pIC50 8.7 [101]
GRN-529 Small molecule or natural product Hs Negative 8.6 pIC50 39
⤷ pIC50 8.6 (IC50 2.6x10-9 M) [39]
compound 8 [PMID: 15482908] Small molecule or natural product Hs Negative 8.4 pIC50 91
⤷ pIC50 8.4 (IC50 3.9x10-9 M) [91]
[3H]M-MPEP Small molecule or natural product Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Negative 8.3 – 8.4 pIC50 29,66
⤷ pIC50 8.4 [29]
pIC50 8.3 [66]
compound 10 [PMID: 15482906] Small molecule or natural product Hs Negative 8.2 pIC50 37
⤷ pIC50 8.2 (IC50 6.7x10-9 M) [37]
AZD9272 Small molecule or natural product Hs Negative 8.1 pIC50 76
⤷ pIC50 8.1 (IC50 7.6x10-9 M) [76]
alloswitch-1 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Rn Negative 8.1 pIC50 74
⤷ pIC50 8.1 (IC50 8.6x10-9 M) [74]
Description: Inhibition of agonist-induced IP accumulation.
CTEP Small molecule or natural product Hs Negative 7.9 – 8.2 pIC50 48
⤷ pIC50 7.9 – 8.2 (IC50 1.14x10-8 – 6.4x10-9 M) [48]
compound 30 [PMID: 21757343] Small molecule or natural product Rn Negative 7.9 pIC50 102
⤷ pIC50 7.9 (IC50 1.2x10-8 M) [102]
VU0463841 Small molecule or natural product Rn Negative 7.9 pIC50 2
⤷ pIC50 7.9 (IC50 1.3x10-8 M) [2]
AZD6538 Small molecule or natural product Hs Negative 7.9 pIC50 76
⤷ pIC50 7.9 (IC50 1.34x10-8 M) [76]
compound 29b [PMID: 20809633] Small molecule or natural product Hs Negative 7.8 pIC50 12
⤷ pIC50 7.8 (IC50 1.6x10-8 M) [12]
compound 30 [PMID: 21757343] Small molecule or natural product Hs Negative 7.8 pIC50 102
⤷ pIC50 7.8 (IC50 1.7x10-8 M) [102]
compound 24 [PMID: 23374867] Small molecule or natural product Hs Negative 7.7 pIC50 34
⤷ pIC50 7.7 (IC50 1.9x10-8 M) [34]
[14C]MTEP Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Negative 7.7 pIC50 3
⤷ pIC50 7.7 [3]
dipraglurant Small molecule or natural product Hs Negative 7.7 pIC50 15
⤷ pIC50 7.7 (IC50 2x10-8 M) [15]
compound 16a [PMID: 14697765] Small molecule or natural product Hs Negative 7.7 pIC50 101
⤷ pIC50 7.7 (IC50 2.2x10-8 M) [101]
compound 24d [PMID: 23357634] Small molecule or natural product Hs Negative 7.6 pIC50 108
⤷ pIC50 7.6 (IC50 2.3x10-8 M) [108]
VU0285683 Small molecule or natural product Rn Negative 7.6 pIC50 77
⤷ pIC50 7.6 (IC50 2.44x10-8 M) [77]
MPEP Small molecule or natural product Click here for species-specific activity table Hs Negative 7.4 – 7.7 pIC50 29-30
⤷ pIC50 7.4 – 7.7 [29-30]
compound 13 [PMID: 15686941] Small molecule or natural product Hs Negative 7.6 pIC50 6
⤷ pIC50 7.6 (IC50 2.8x10-8 M) [6]
methoxymethyl-MTEP Small molecule or natural product Rn Negative 7.5 pIC50 3
⤷ pIC50 7.5 (IC50 3x10-8 M) [3]
compound 16m [PMID: 19931453] Small molecule or natural product Hs Negative 7.5 pIC50 92
⤷ pIC50 7.5 (IC50 3.2x10-8 M) [92]
compound 11a [PMID: 14697765] Small molecule or natural product Hs Negative 7.4 pIC50 101
⤷ pIC50 7.4 (IC50 4.1x10-8 M) [101]
GSK2210875 Small molecule or natural product Hs Negative 7.4 pIC50 71
⤷ pIC50 7.4 (IC50 4x10-8 M) [71]
compound 53 [PMID: 23434029] Small molecule or natural product Hs Negative 7.4 pIC50 15
⤷ pIC50 7.4 (IC50 4x10-8 M) [15]
compound 27 [PMID: 20598884] Small molecule or natural product Rn Negative 7.3 pIC50 25
⤷ pIC50 7.3 (IC50 4.5x10-8 M) [25]
compound 36 [PMID: 17936624] Small molecule or natural product Rn Negative 7.3 pIC50 27
⤷ pIC50 7.3 (IC50 5.17x10-8 M) [27]
compound 8 [PMID: 20598884] Small molecule or natural product Rn Negative 7.2 pIC50 25
⤷ pIC50 7.2 (IC50 5.9x10-8 M) [25]
compound 42 [PMID: 17189691] Small molecule or natural product Rn Negative 7.2 pIC50 14
⤷ pIC50 7.2 (IC50 6x10-8 M) [14]
compound 18 [PMID: 21927650] Small molecule or natural product Hs Negative 7.2 pIC50 49
⤷ pIC50 7.2 (IC50 6.1x10-8 M) [49]
PTeB Small molecule or natural product Hs Negative 7.2 pIC50 84
⤷ pIC50 7.2 [84]
fenobam Small molecule or natural product Ligand has a PDB structure Hs Negative 7.2 pIC50 75
⤷ pIC50 7.2 [75]
compound 10 [PMID: 15482908] Small molecule or natural product Hs Negative 7.1 pIC50 91
⤷ pIC50 7.1 (IC50 7.7x10-8 M) [91]
3,3'-difluorobenzaldazine Small molecule or natural product Hs Positive 5.6 – 8.5 pIC50 66-67
⤷ pIC50 5.6 – 8.5 [66-67]
VU0366058 Small molecule or natural product Rn Negative 7.0 pIC50 62
⤷ pIC50 7.0 (IC50 9.1x10-8 M) [62]
ADX-47273 Small molecule or natural product Rn Positive 6.5 pIC50 47
⤷ pIC50 6.5 [47]
CPPHA Small molecule or natural product Hs Positive 6.3 pIC50 67
⤷ pIC50 6.3 [67]
SIB-1757 Small molecule or natural product Hs Negative 6.0 – 6.4 pIC50 29,99
⤷ pIC50 6.0 – 6.4 [29,99]
SIB-1893 Small molecule or natural product Click here for species-specific activity table Hs Negative 5.9 – 6.5 pIC50 29,99
⤷ pIC50 5.9 – 6.5 [29,99]
View species-specific allosteric modulator tables
Allosteric Modulator Comments
M-5MPEP is a partal antagonist at the rat receptor [78].

Allosteric regulators, either negative (non-competitive antagonists), positive (allosteric potentiators), or neutral, are usually highly selective for mGlu5, being inactive on the highly homologous mGlu1 receptor. These modulators bind in the 7TM region of the receptor [54,68], whereas the orthosteric site is located in the large extracellular domain of this receptor. A second important point is that many negative modulators possess inverse agonist activity. However, allosteric "partial antagonists" have now been discovered [78]. The concept of partial antagonist activity is novel and can only be achieved with compounds acting at an allosteric site. Although a clear interaction between DFB, CDPPB and the MPEP binding site has been described, the relationship between binding to this site and allosteric potentiation is not yet clear. CPPHA clearly binds at a site different from MPEP [67]. DCB and 5MPEP have been shown to inhibit the effect of both positive and negative allosteric modulators, and represents as such a novel type of modulator called a neutral allosteric site ligand [66,78].

M-5MPEP and Br5-MPEPy fully displace binding of [3H]methoxyPEPy but do not fully block glutamate responses [78]. VU0357121 binds to a site other than the MPEP site [33].

VU0365396 is a non-MPEP site, neutral allosteric ligand [33]. [18F]FPEB has been used in receptor occupancy in humans [96,104].
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
Comments:  The main action of mGlu5 is to activate PLC via Gq/11. This can be measured via the inositol phosphate production or increase in intracelular Ca2+ both in cell lines expressing this recombinant receptor or in native tissue such as brain slices or cultured neurons or astrocytes.
References:  18,73
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family
Gi/Go family 		Adenylyl cyclase stimulation
Potassium channel
Calcium channel
Phospholipase A2 stimulation
Phospholipase D stimulation
Other - See Comments
Comments:  Stimulation of adenylyl cyclase has been reported in transfected cell lines, and in native tissue although it is not yet known whether this effect is due to mGlu5 or mGlu1 or both [18].

Coupling of group-I mGlu receptors to PTX-sensitive G-proteins Gi and Go has also been observed in many cells including neurons. Such a coupling is at the origin of MAPK activation.

Activation of PLA2 is potentiated by co-activation of the NMDA receptor [24].

PLD activation has been reported both in brain slices [46] and in cultured astrocytes [86]. However, some studies reported this response may also be generated by an mglu receptor with specific pharmacological properties [7,18].

Activation of big potassium currents likely results from the increase in intracellular Ca2+. However, inhibition of various type of potassium currents lead to an increase in cell excitability [4].

Both inhibition and potentiation of voltage sensitive Ca2+ channels (N and L types) have been reported [4,18,73].
References:  4,18,73
Tissue Distribution Click here for help
Islets of Langerhans and in pancreatic alpha-cell and beta-cell lines.
Species:  Human
Technique:  RT-PCR and immunoblot.
References:  9
Testes.
Species:  Human
Technique:  immunocytochemistry.
References:  95
Melanocytes.
Species:  Human
Technique:  RT-PCR and immunocytochemistry.
References:  26
Thymus, isolated thymocytes and TC-1S thymic stromal cell line, CD4(+) CD8(+) and CD4(+)CD8(-) thymocytes.
Species:  Mouse
Technique:  RT-PCR and immunoblot.
References:  94
Retina.
Species:  Rat
Technique:  in situ hybridisation.
References:  35
Olefactory bulb, anterior olfactory nucleus, accumbens nucleus, olafactory tubercle, striatum, hippocampus, subiculum, cerebral cortex, lateral septal nucleus, inferior culliculus, cerebellar cortex, spinal trigeminal nucleus, thalamus, ventromedial hypothalamic nucleus.
Species:  Rat
Technique:  in situ hybridization.
References:  1
Olfactory bulb, anterior olfactory nuclei, olfactory tubercle, cerebral cortex, hippocampus, lateral septum, striatum, nucleus accumbens, inferior colliculus, and spinal trigeminal nuclei.
Species:  Rat
Technique:  Immunohistochemistry.
References:  88
Pinealocytes.
Species:  Rat
Technique:  RT-PCR, Northern blot.
References:  106
mGlu5 was rarely detected in pre-synaptic elements.
Species:  Rat
Technique:  immunocytochemistry.
References:  80
At the subcellular level, mGlu5 was found in post-synaptic elements on the side of the post-synaptic density.
Species:  Rat
Technique:  immunocytochemistry.
References:  52-53,80
Islets of Langerhans and pancreatic alpha-cell and beta-cell lines.
Species:  Rat
Technique:  RT-PCR and immunoblot.
References:  9
Suprachiasmatic nucleus, preoptic area, lateral hypothalamus, and mammillary region, ventromedial nucleus.
Species:  Rat
Technique:  Western and Northern blot.
References:  97
Brain.
Species:  Rat
Technique:  RT-PCR, Western blot, immunocytochemistry.
References:  81
Neostriatum, neocortex, and hippocampus.
Species:  Rat
Technique:  in situ hybridization.
References:  42
mGlu5 is found on both astrocytes and neurons, with most intense expression in the olfactory bulb (granule cells), cerebral cortex, hippocampus (dentate gyrus and pyramidal neurons of the CA1-3 area) lateral septum, striatum, nucleus accumbens and inferior colliculus. In the cerebellum, mGlu5 receptors are expressed only in a sub-population of Golgi neurons.
Species:  Rat
Technique:  immunocytochemistry.
References:  80,87
Testes.
Species:  Rat
Technique:  RT-PCR.
References:  95
mGlu5 receptors have also been detected outside the brain, especially in peripheral unmyelinated sensory afferent terminals.
Species:  Rat
Technique:  immunocytochemistry.
References:  5,90
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
Measurement of IP levels in cultured rat astrocytes treated with EGF.
Species:  Rat
Tissue:  Cultured cortical astrocytes.
Response measured:  IP formation.
References:  59
Measurement of intracellular IP and Ca2+ levels in CHO cells transfected with rat mGlu5 receptors.
Species:  Rat
Tissue:  CHO cells.
Response measured:  IP formation and increase in Ca2+ levels.
References:  1
Measurement of intracellular IP and Ca2+ levels in HEK 293 cells transfected with rat mGlu5 receptor.
Species:  Rat
Tissue:  HEK 293 cells.
Response measured:  IP formation and increase in Ca2+ levels.
References:  8,21
Measurement of IP formation in an RGT cell line transfected with the human mGlu5 receptor.
Species:  Human
Tissue:  RGT cell line.
Response measured:  IP formation.
References:  43
Measurement of Ca2+ levels and ERK phosphorylation in rat cultured cortical astrocytes.
Species:  Rat
Tissue:  Cultured cortical astrocytes.
Response measured:  Increase in Ca2+ levels and ERK phosphorylation.
References:  70,107
Physiological Functions Click here for help
mGlu5 receptor activation facilitates LTP induction in the CA1 area and dentate gyrus of the hippocampus
Species:  Mouse
Tissue:  Hippocampal slices.
References:  51
Presynaptic control of neurotransmitter release in various brain areas. This is likely to be indirect, being a consequence of endogenous cannabinoid release from the post-synaptic element.
Species:  Mouse
Tissue:  Hippocampal slices
References:  79
Astrocytic mGlu5 is likely responsible for functional hyperemia - the coupling of neuronal activation to cerebral blood vessel responses
Species:  Rat
Tissue:  Cortical slices
References:  110
mGlu5 receptors in the periphery are involved in the sensation of inflammatory pain.
Species:  Rat
Tissue:  Skin.
References:  5,100
mGlu5 receptor activation facilitates LTP induction and can induce LTD in the CA1 area and dentate gyrus of the hippocampus.
Species:  Rat
Tissue:  Hippocampal slices.
References:  28
mGlu5 receptor activation acts postsynaptically to regulate ion channels and increase excitability of many neuronal populations throughout the CNS.
Species:  Rat
Tissue:  Hippocampal slices.
References:  57
Physiological Consequences of Altering Gene Expression Click here for help
mGlu5 receptor knockout mice exhibit disruption of prepulse inhibition.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  11
mGlu5 receptor knockout mice exhibit impaired acquisition and use of spatial information in both the Morris water maze and contextual information in the fear-conditioning test.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  51
mGlu5 receptor knockout mice exhibit impaired CA1 LTP.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  51
mGlu5 receptor knockout mice exhibit a loss of cocaine self administration.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  17
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
Grm5tm1Fcq Grm5tm1Fcq/Grm5tm1Fcq
Not Specified		 MGI:1351342  MP:0002556 abnormal cocaine consumption PMID: 11528416 
Grm5tm1Rod Grm5tm1Rod/Grm5tm1Rod
involves: 129S1/Sv * 129X1/SvJ * CD-1		 MGI:1351342  MP:0001469 abnormal contextual conditioning behavior PMID: 9185557 
Grm5tm1.2Jixu Grm5tm1.2Jixu/Grm5tm1.2Jixu
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6		 MGI:1351342  MP:0001469 abnormal contextual conditioning behavior PMID: 19321764 
Grm5tm1.2Jixu Grm5tm1.2Jixu/Grm5tm1.2Jixu
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6		 MGI:1351342  MP:0001454 abnormal cued conditioning behavior PMID: 19321764 
Grm5tm1Rod Grm5tm1Rod/Grm5tm1Rod
involves: 129S1/Sv * 129X1/SvJ * CD-1		 MGI:1351342  MP:0002912 abnormal excitatory postsynaptic potential PMID: 9185557 
Grm5tm1.2Jixu Grm5tm1.2Jixu/Grm5tm1.2Jixu
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6		 MGI:1351342  MP:0006299 abnormal latent inhibition of conditioning behavior PMID: 19321764 
Grm5tm1.2Jixu Grm5tm1.2Jixu/Grm5tm1.2Jixu
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6		 MGI:1351342  MP:0001449 abnormal learning/ memory PMID: 19321764 
Grm5tm1Rod Grm5tm1Rod/Grm5tm1Rod
B6.129-Grm5/J		 MGI:1351342  MP:0003313 abnormal locomotor activation PMID: 16280580 
Grm5+|Grm5tm1Rod Grm5tm1Rod/Grm5+
involves: 129 * C57BL/6 * FVB		 MGI:1351342  MP:0003477 abnormal nerve fiber response PMID: 18093519 
Grm5tm1Rod Grm5tm1Rod/Grm5tm1Rod
involves: 129S1/Sv * 129X1/SvJ * CD-1		 MGI:1351342  MP:0001463 abnormal spatial learning PMID: 9185557 
Fmr1tm1Cgr|Grm5+|Grm5tm1Rod Fmr1tm1Cgr/Y,Grm5tm1Rod/Grm5+
involves: 129P2/OlaHsd * C57BL/6 * FVB		 MGI:1351342  MGI:95564  MP:0001496 audiogenic seizures PMID: 18093519 
Grm5tm1.1Kksz Grm5tm1.1Kksz/Grm5tm1.1Kksz
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:1351342  MP:0003546 decreased alcohol consumption PMID: 19587272 
Grm5tm1Fcq Grm5tm1Fcq/Grm5tm1Fcq
Not Specified		 MGI:1351342  MP:0009758 impaired behavioral response to cocaine PMID: 11528416 
Fmr1tm1Cgr|Grm5+|Grm5tm1Rod Fmr1tm1Cgr/Y,Grm5tm1Rod/Grm5+
involves: 129P2/OlaHsd * C57BL/6 * FVB		 MGI:1351342  MGI:95564  MP:0004851 increased testis weight PMID: 18093519 
Grm5tm1Rod Grm5tm1Rod/Grm5tm1Rod
involves: 129S1/Sv * 129X1/SvJ * CD-1		 MGI:1351342  MP:0001473 reduced long term potentiation PMID: 9185557 
Grm5tm1Fcq Grm5tm1Fcq/Grm5tm1Fcq
Not Specified		 MGI:1351342  MP:0001473 reduced long term potentiation PMID: 12559117 
Biologically Significant Variants Click here for help
Type:  Splice variants
Species:  Rat
Description:  mGlu5(b) possesses an additional 32 amino acid residues inserted after L875, 49 residues after the 7th TM . No functional differences have been reported so far between these two variants. In addition two types of mGlu5 transcripts with different 5' untranslated sequences are also generated due to two distinct transcription initiation signals, allowing for different regulation of mGlu5 expression in various cell types.
References:  1,41,105
Type:  Splice variants
Species:  Human
Description:  Both mGlu5(a) and mGlu5(b) as well as the use of two distinct initiation signals have been identified in human.
References:  19,60-61

References

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