mGlu<sub>5</sub> receptor | Metabotropic glutamate receptors | IUPHAR/BPS Guide to PHARMACOLOGY

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mGlu5 receptor

Target not currently curated in GtoImmuPdb

Target id: 293

Nomenclature: mGlu5 receptor

Family: Metabotropic glutamate receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

Gene and Protein Information
class C G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 1212 11q14.2 GRM5 glutamate metabotropic receptor 5 59-60
Mouse 7 1203 7 D3 Grm5 glutamate receptor, metabotropic 5
Rat 7 1203 1q32 Grm5 glutamate metabotropic receptor 5 1,40
Previous and Unofficial Names
mGluR5 | GPRC1E | glutamate receptor
Database Links
Specialist databases
GPCRDB grm5_human (Hs), grm5_mouse (Mm), grm5_rat (Rn)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
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
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 Value Parameter Reference
VU0424465 Rn Agonist 6.8 pEC50 81
pEC50 6.8 (EC50 1.71x10-7 M) [81]
VU0092273 Rn Agonist 5.9 pEC50 64
pEC50 5.9 (EC50 1.3x10-6 M) [64]
L-glutamic acid Hs Agonist 5.0 – 5.5 pEC50 71
pEC50 5.0 – 5.5 [71]
(S)-(+)-CBPG Rn Partial agonist 4.3 pEC50 55
pEC50 4.3 (EC50 4.7x10-5 M) [55]
quisqualate Rn Full agonist 7.5 pIC50 62
pIC50 7.5 [62]
L-glutamic acid Rn Full agonist 6.1 pIC50 62
pIC50 6.1 [62]
L-CCG-I Rn Full agonist 5.8 pIC50 62
pIC50 5.8 [62]
(1S,3R)-ACPD Rn Full agonist 5.7 pIC50 62
pIC50 5.7 [62]
ibotenic acid Rn Full agonist 5.7 pIC50 62
pIC50 5.7 [62]
3,5-DHPG Rn Partial agonist 5.4 pIC50 62
pIC50 5.4 [62]
(S)-3HPG Rn Partial agonist 5.0 pIC50 62
pIC50 5.0 [62]
CHPG Hs Full agonist 3.4 pIC50 62
pIC50 3.4 [62]
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 [83]. 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 Rn Antagonist 5.6 pKi 37
pKi 5.6 (Ki 2.366x10-6 M) [37]
methoxy-MPEP Hs Antagonist 8.4 pIC50 29
pIC50 8.4 (IC50 3.6x10-9 M) [29]
Description: [3H]-M-MPEP displacement assay.
ACDPP Hs Antagonist 6.9 pIC50 6
pIC50 6.9 [6]
(S)-4C3HPG Rn Antagonist 5.6 pIC50 62
pIC50 5.6 [62]
LY341495 Hs Antagonist 5.1 pIC50 43
pIC50 5.1 [43]
DCG-IV Rn Antagonist 4.7 pIC50 62
pIC50 4.7 [62]
(S)-4CPG Rn Antagonist 4.6 pIC50 62
pIC50 4.6 [62]
(+)-MCPG Rn Antagonist 3.7 pIC50 62
pIC50 3.7 [62]
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 [83]. 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 [83]). (S)-4C3HPG has been reported to have slight partial agonist activity at this receptor [40].
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
VU0483605 Rn Positive 6.5 pKB 35
pKB 6.5 [35]
GS39783 Rn Neutral 6.3 pKB 35
pKB 6.3 [35]
PHCCC Rn Neutral 5.6 pKB 35
pKB 5.6 [35]
AZ12216052 Rn Positive 5.4 pKB 35
pKB 5.4 [35]
NPS 2143 Rn Positive 5.1 pKB 35
pKB 5.1 [35]
CPCCOEt Rn Neutral 4.9 pKB 35
pKB 4.9 [35]
CGP7930 Rn Positive 4.8 pKB 35
pKB 4.8 [35]
[3H]CTEP Rn Negative 8.8 pKd 47
pKd 8.8 (Kd 1.5x10-9 M) [47]
[3H]CTEP Hs Negative 8.8 pKd 47
pKd 8.8 (Kd 1.7x10-9 M) [47]
[3H]CTEP Mm Negative 8.7 pKd 47
pKd 8.7 (Kd 1.8x10-9 M) [47]
[3H]methoxy-PEPy Rn Negative 8.5 pKd 20
pKd 8.5 (Kd 3.4x10-9 M) [20]
[3H]methoxymethyl-MTEP Rn Negative 7.7 pKd 20
pKd 7.7 (Kd 2x10-8 M) [20]
[3H]fenobam Hs Negative 7.5 pKd 74
pKd 7.5 [74]
[3H]fenobam Rn Negative 7.3 pKd 74
pKd 7.3 [74]
compound 20 [PMID: 16439120] Rn Negative 9.0 pKi 13
pKi 9.0 (Ki 1x10-9 M) [13]
BOMA Hs Negative 8.5 pKi 99
pKi 8.5 [99]
AZD9272 Hs Negative 8.4 pKi 75
pKi 8.4 (Ki 3.8x10-9 M) [75]
GRN-529 Rn Negative 8.3 pKi 38
pKi 8.3 (Ki 5.4x10-9 M) [38]
CTEP Mm Negative 8.0 pKi 47
pKi 8.0 (Ki 9.5x10-9 M) [47]
compound 26 [PMID: 16439120] Rn Negative 8.0 pKi 13
pKi 8.0 (Ki 1x10-8 M) [13]
compound 30 [PMID: 21757343] Hs Negative 7.9 pKi 100
pKi 7.9 (Ki 1.2x10-8 M) [100]
compound 10 [PMID: 15482906] Hs Negative 7.9 pKi 36
pKi 7.9 (Ki 1.2x10-8 M) [36]
CTEP Rn Negative 7.9 pKi 47
pKi 7.9 (Ki 1.26x10-8 M) [47]
compound 8 [PMID: 15482908] Rn Negative 7.8 pKi 89
pKi 7.8 (Ki 1.4x10-8 M) [89]
MTEP Hs Negative 7.8 pKi 10
pKi 7.8 (Ki 1.6x10-8 M) [10]
VU0285683 Rn Negative 7.8 pKi 76
pKi 7.8 (Ki 1.6x10-8 M) [76]
compound 29b [PMID: 20809633] Rn Negative 7.8 pKi 12
pKi 7.8 (Ki 1.7x10-8 M) [12]
CTEP Hs Negative 7.7 – 7.8 pKi 39,47
pKi 7.7 – 7.8 (Ki 2x10-8 – 1.64x10-8 M) [39,47]
compound 10 [PMID: 15482908] Rn Negative 7.7 pKi 89
pKi 7.7 (Ki 1.9x10-8 M) [89]
compound 23 [PMID: 17590335] Rn Negative 7.7 pKi 57
pKi 7.7 (Ki 2.2x10-8 M) [57]
AZD6538 Hs Negative 7.6 pKi 75
pKi 7.6 (Ki 2.8x10-8 M) [75]
compound 24d [PMID: 23357634] Rn Negative 7.5 pKi 106
pKi 7.5 (Ki 3x10-8 M) [106]
basimglurant Hs Negative 7.4 pKi 39
pKi 7.4 (Ki 3.6x10-8 M) [39]
Description: Reduction of antagonist MPEP binding to mGlu5 receptors in vitro
compound 16m [PMID: 19931453] Hs Negative 7.4 pKi 90
pKi 7.4 (Ki 3.8x10-8 M) [90]
VU0366058 Rn Negative 7.1 pKi 61
pKi 7.1 (Ki 8.4x10-8 M) [61]
compound 16a [PMID: 14697765] Rn Negative 7.0 pKi 99
pKi 7.0 (Ki 9.1x10-8 M) [99]
compound 42 [PMID: 17189691] Rn Negative 7.0 pKi 14
pKi 7.0 (Ki 9.5x10-8 M) [14]
compound 8 [PMID: 20598884] Rn Negative 7.0 pKi 25
pKi 7.0 (Ki 1.02x10-7 M) [25]
VU-1545 Rn Positive 6.8 pKi 22
pKi 6.8 (Ki 1.56x10-7 M) [22]
compound 11a [PMID: 14697765] Rn Negative 6.8 pKi 99
pKi 6.8 (Ki 1.59x10-7 M) [99]
VU0360172 Rn Positive 6.7 pKi 76
pKi 6.7 (Ki 1.95x10-7 M) [76]
compound 27 [PMID: 20598884] Rn Negative 6.7 pKi 25
pKi 6.7 (Ki 2.06x10-7 M) [25]
VU-29 Rn Positive 6.6 pKi 16
pKi 6.6 (Ki 2.44x10-7 M) [16]
M-5MPEP Rn Negative 6.5 pKi 77
pKi 6.5 (Ki 3x10-7 M) [77]
Br-5MPEPy Rn Negative 6.5 pKi 77
pKi 6.5 (Ki 3x10-7 M) [77]
LSN2463359 Rn Positive 6.4 pKi 31
pKi 6.4 (Ki 3.77x10-7 M) [31]
5-MPEP Rn Neutral 6.4 pKi 77
pKi 6.4 [77]
compound 18 [PMID: 21927650] Rn Negative 6.3 pKi 48
pKi 6.3 (Ki 4.77x10-7 M) [48]
LSN2814617 Rn Positive 5.9 pKi 31
pKi 5.9 (Ki 1.34x10-6 M) [31]
5PAM523 Rn Positive 5.7 pKi 68
pKi 5.7 (Ki 2x10-6 M) [68]
CPPZ Rn Positive 5.5 pKi 91
pKi 5.5 (Ki 3.1x10-6 M) [91]
ADX-47273 Rn Positive 5.4 pKi 31
pKi 5.4 (Ki 3.65x10-6 M) [31]
cinacalcet Rn Positive 4.3 pKi 35
pKi 4.3 [35]
VU0424465 Rn Positive 8.8 pEC50 81
pEC50 8.8 (EC50 1.5x10-9 M) [81]
VU0404251 Rn Positive 8.1 pEC50 54
pEC50 8.1 (EC50 7.2x10-9 M) [54]
VU-29 Rn Positive 8.1 pEC50 16
pEC50 8.1 (EC50 9x10-9 M) [16]
VU-1545 Hs Positive 8.0 pEC50 22
pEC50 8.0 (EC50 9.6x10-9 M) [22]
VU0463841 Rn Negative 7.9 pEC50 2
pEC50 7.9 (EC50 1.3x10-8 M) [2]
compound 41 [PMID: 23434029] Hs Negative 7.9 pEC50 15
pEC50 7.9 (EC50 1.3x10-8 M) [15]
CDPPB Hs Positive 7.6 – 8.0 pEC50 44,49
pEC50 7.6 – 8.0 [44,49]
VU0360172 Rn Positive 7.8 pEC50 76
pEC50 7.8 (EC50 1.6x10-8 M) [76]
CDPPB Rn Positive 7.7 pEC50 49
pEC50 7.7 [49]
LSN2463359 Rn Positive 7.6 pEC50 31
pEC50 7.6 (EC50 2.4x10-8 M) [31]
LSN2463359 Hs Positive 7.5 pEC50 31
pEC50 7.5 (EC50 3.3x10-8 M) [31]
VU0357121 Rn Positive 7.5 pEC50 32
pEC50 7.5 (EC50 3.3x10-8 M) [32]
VU0092273 Rn Positive 7.5 pEC50 64
pEC50 7.5 (EC50 3.5x10-8 M) [64]
VU0240382 Rn Positive 7.4 pEC50 64
pEC50 7.4 (EC50 3.9x10-8 M) [64]
compound 47 [PMID: 21295468] Hs Positive 7.3 pEC50 96
pEC50 7.3 (EC50 5.01x10-8 M) [96]
LSN2814617 Hs Positive 7.3 pEC50 31
pEC50 7.3 (EC50 5.2x10-8 M) [31]
ADX-47273 Rn Positive 7.3 pEC50 31
pEC50 7.3 (EC50 5.5x10-8 M) [31]
VU0404251 Hs Positive 7.2 pEC50 54
pEC50 7.2 (EC50 7x10-8 M) [54]
LSN2814617 Rn Positive 7.0 pEC50 31
pEC50 7.0 (EC50 9.3x10-8 M) [31]
VU0361747 Rn Positive 6.9 pEC50 64
pEC50 6.9 (EC50 1.26x10-7 M) [64]
ADX-47273 Hs Positive 6.8 pEC50 31
pEC50 6.8 (EC50 1.57x10-7 M) [31]
5PAM523 Hs Positive 6.7 pEC50 68
pEC50 6.7 (EC50 2.01x10-7 M) [68]
5PAM523 Rn Positive 6.5 pEC50 68
pEC50 6.5 (EC50 3.11x10-7 M) [68]
NCFP Rn Positive 6.0 – 6.7 pEC50 63
pEC50 6.7 (EC50 2.14x10-7 M) EC50 with high mGlu5 expression [63]
pEC50 6.4 (EC50 3.7x10-7 M) EC50 with low mGlu5 expression [63]
pEC50 6.0 (EC50 9.69x10-7 M) EC50 from assay using rat astrocytes [63]
CPPZ Hs Positive 6.3 pEC50 91
pEC50 6.3 (EC50 5x10-7 M) [91]
VU0364289 Rn Positive 5.8 pEC50 107
pEC50 5.8 (EC50 1.6x10-6 M) [107]
SP203 Rn Negative 10.4 pIC50 87
pIC50 10.4 (IC50 3.6x10-11 M) [87]
compound 18 [PMID: 17723296] Rn Negative 9.1 pIC50 101
pIC50 9.1 (IC50 7.2x10-10 M) [101]
compound 23 [PMID: 17590335] Rn Negative 9.1 pIC50 57
pIC50 9.1 (IC50 8x10-10 M) [57]
MTEB Hs Negative 8.7 pIC50 99
pIC50 8.7 [99]
GRN-529 Hs Negative 8.6 pIC50 38
pIC50 8.6 (IC50 2.6x10-9 M) [38]
compound 8 [PMID: 15482908] Hs Negative 8.4 pIC50 89
pIC50 8.4 (IC50 3.9x10-9 M) [89]
[3H]M-MPEP Hs Negative 8.3 – 8.4 pIC50 29,65
pIC50 8.4 [29]
pIC50 8.3 [65]
compound 10 [PMID: 15482906] Hs Negative 8.2 pIC50 36
pIC50 8.2 (IC50 6.7x10-9 M) [36]
AZD9272 Hs Negative 8.1 pIC50 75
pIC50 8.1 (IC50 7.6x10-9 M) [75]
alloswitch-1 Rn Negative 8.1 pIC50 73
pIC50 8.1 (IC50 8.6x10-9 M) [73]
Description: Inhibition of agonist-induced IP accumulation.
CTEP Hs Negative 7.9 – 8.2 pIC50 47
pIC50 7.9 – 8.2 (IC50 1.14x10-8 – 6.4x10-9 M) [47]
compound 30 [PMID: 21757343] Rn Negative 7.9 pIC50 100
pIC50 7.9 (IC50 1.2x10-8 M) [100]
VU0463841 Rn Negative 7.9 pIC50 2
pIC50 7.9 (IC50 1.3x10-8 M) [2]
AZD6538 Hs Negative 7.9 pIC50 75
pIC50 7.9 (IC50 1.34x10-8 M) [75]
compound 29b [PMID: 20809633] Hs Negative 7.8 pIC50 12
pIC50 7.8 (IC50 1.6x10-8 M) [12]
compound 30 [PMID: 21757343] Hs Negative 7.8 pIC50 100
pIC50 7.8 (IC50 1.7x10-8 M) [100]
compound 24 [PMID: 23374867] Hs Negative 7.7 pIC50 33
pIC50 7.7 (IC50 1.9x10-8 M) [33]
[14C]MTEP Rn Negative 7.7 pIC50 3
pIC50 7.7 [3]
dipraglurant Hs Negative 7.7 pIC50 15
pIC50 7.7 (IC50 2x10-8 M) [15]
compound 16a [PMID: 14697765] Hs Negative 7.7 pIC50 99
pIC50 7.7 (IC50 2.2x10-8 M) [99]
compound 24d [PMID: 23357634] Hs Negative 7.6 pIC50 106
pIC50 7.6 (IC50 2.3x10-8 M) [106]
VU0285683 Rn Negative 7.6 pIC50 76
pIC50 7.6 (IC50 2.44x10-8 M) [76]
MPEP Hs Negative 7.4 – 7.7 pIC50 29-30
pIC50 7.4 – 7.7 [29-30]
compound 13 [PMID: 15686941] Hs Negative 7.6 pIC50 6
pIC50 7.6 (IC50 2.8x10-8 M) [6]
methoxymethyl-MTEP Rn Negative 7.5 pIC50 3
pIC50 7.5 (IC50 3x10-8 M) [3]
compound 16m [PMID: 19931453] Hs Negative 7.5 pIC50 90
pIC50 7.5 (IC50 3.2x10-8 M) [90]
compound 11a [PMID: 14697765] Hs Negative 7.4 pIC50 99
pIC50 7.4 (IC50 4.1x10-8 M) [99]
GSK2210875 Hs Negative 7.4 pIC50 70<