M2 receptor

Target id: 14

Nomenclature: M2 receptor

Family: Acetylcholine receptors (muscarinic)

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

   GtoImmuPdb view: OFF :     Currently no data for M2 receptor in GtoImmuPdb

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 466 7q31-q35 CHRM2 cholinergic receptor muscarinic 2 2,9-10,95,145
Mouse 7 466 6 B1 Chrm2 cholinergic receptor 75
Rat 7 466 4q22 Chrm2 cholinergic receptor 125
Previous and Unofficial Names
M2 muscarinic acetylcholine receptor | Chrm-2 | AChR M2 | cholinergic receptor, muscarinic 2 | cholinergic receptor | cholinergic receptor, muscarinic 2, cardiac
Database Links
Specialist databases
GPCRDB acm2_human (Hs), acm2_mouse (Mm), acm2_rat (Rn)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist
PDB Id:  3UON
Ligand:  3-quinuclidinyl-benzilate
Resolution:  3.0Å
Species:  Human
References:  43
Image of receptor 3D structure from RCSB PDB
Description:  Structure of active human M2 muscarinic acetylcholine receptor bound to the agonist iperoxo
PDB Id:  4MQS
Ligand:  iperoxo
Resolution:  3.5Å
Species:  Human
References:  61
Image of receptor 3D structure from RCSB PDB
Description:  Structure of active human M2 muscarinic acetylcholine receptor bound to the agonist iperoxo and allosteric modulator LY2119620
PDB Id:  4MQT
Ligand:  LY2119620
Resolution:  3.7Å
Species:  Human
References:  61
Natural/Endogenous Ligands
acetylcholine

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]acetylcholine Hs Agonist 8.8 pKd 67
pKd 8.8 [67]
[3H]oxotremorine-M Hs Full agonist 8.7 pKd 5
pKd 8.7 [5]
NNC 11-1585 Hs Full agonist 10.1 pKi 21
pKi 10.1 [21]
NNC 11-1607 Hs Full agonist 8.2 pKi 21
pKi 8.2 [21]
pentylthio-TZTP Hs Full agonist 7.9 pKi 55
pKi 7.9 [55]
methacholine Rn Agonist 7.2 pKi 93
pKi 7.2 (Ki 5.9x10-8 M) [93]
NNC 11-1314 Hs Full agonist 7.2 pKi 21
pKi 7.2 [21]
xanomeline Hs Full agonist 6.9 – 7.4 pKi 133,140
pKi 6.9 – 7.4 [133,140]
oxotremorine Rn Full agonist 6.5 pKi 60
pKi 6.5 [60]
acetylcholine Rn Full agonist 6.4 pKi 60
pKi 6.4 [60]
cevimeline Hs Agonist 6.1 pKi 73
pKi 6.1 (Ki 8.54x10-7 M) [73]
Description: Displacement of [3H]QNB from cloned receptor.
oxotremorine Hs Full agonist 5.0 – 6.6 pKi 55,60
pKi 5.0 – 6.6 [55,60]
arecaidine propargyl ester Hs Full agonist 5.7 pKi 55
pKi 5.7 [55]
carbachol Rn Full agonist 5.7 pKi 60
pKi 5.7 [60]
acetylcholine Hs Full agonist 4.3 – 6.5 pKi 20,55,60,66
pKi 4.3 – 6.5 [20,55,60,66]
McN-A-343 Rn Partial agonist 4.7 – 6.0 pKi 64
pKi 4.7 – 6.0 [64]
arecoline Hs Full agonist 5.2 pKi 55
pKi 5.2 [55]
carbachol Hs Full agonist 4.2 – 5.7 pKi 20,55,60
pKi 4.2 – 5.7 [20,55,60]
methylfurmethide Hs Full agonist 4.9 pKi 55
pKi 4.9 [55]
oxotremorine-M Hs Full agonist 4.9 pKi 55
pKi 4.9 [55]
pilocarpine Hs Partial agonist 4.9 pKi 55
pKi 4.9 [55]
furtrethonium Hs Full agonist 4.5 pKi 55
pKi 4.5 [55]
bethanechol Hs Full agonist 4.0 pKi 55
pKi 4.0 [55]
iperoxo Hs Full agonist 9.8 pEC50 104
pEC50 9.8 [104]
(+)-aceclidine Hs Full agonist 6.2 – 6.4 pEC50 31,42
pEC50 6.2 – 6.4 [31,42]
(-)-aceclidine Hs Partial agonist 5.6 – 5.7 pEC50 31,42
pEC50 5.6 – 5.7 [31,42]
[18F]FP-TZTP Mm Full agonist - - 54
[54]
View species-specific agonist tables
Agonist Comments
The binding data for McN-A-343 [64] is found on rat heart.
Please consult references [12,68,100,132,139] for further details of the activity of some of the ligands in this list.
Pilocarpine has been found to be a partial agonist [68,139] and a full agonist [132] at the M2 receptor.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
muscarinic toxin 3 Hs Antagonist >6.3 pA2 91
pA2 >6.3 [91]
[3H]QNB Hs Antagonist 10.1 – 10.6 pKd 95
pKd 10.1 – 10.6 (Kd 7.94x10-11 – 2.51x10-11 M) [95]
[3H]tiotropium Hs Antagonist 10.3 pKd 102
pKd 10.3 [102]
[3H]N-methyl scopolamine Hs Antagonist 9.3 – 9.9 pKd 18,20,47,55-57,59,66,132
pKd 9.3 – 9.9 (Kd 5.2x10-10 – 1.4x10-10 M) [18,20,47,55-57,59,66,132]
[3H]clidinium Hs Antagonist 9.6 pKd 60
pKd 9.6 [60]
[3H]N-methyl scopolamine Rn Antagonist 9.5 pKd 113
pKd 9.5 [113]
[3H]clidinium Rn Antagonist 9.5 pKd 60
pKd 9.5 [60]
[3H]4NMPB Rn Antagonist 9.4 pKd 113
pKd 9.4 [113]
[3H]AF DX-384 Hs Antagonist 8.7 pKd 82
pKd 8.7 [82]
biperiden Hs Antagonist 8.2 pKd 8
pKd 8.2 (Kd 6.3x10-9 M) [8]
Cy3B-telenzepine Hs Antagonist 10.4 pKi 87
pKi 10.4 [87]
tiotropium Hs Antagonist 9.9 pKi 27
pKi 9.9 [27]
umeclidinium Hs Antagonist 9.8 pKi 63,102
pKi 9.8 (Ki 1.5x10-10 M) [63,102]
tripitramine Hs Antagonist 9.6 pKi 74
pKi 9.6 [74]
propantheline Hs Antagonist 9.5 pKi 49
pKi 9.5 [49]
THRX160209 Hs Antagonist 9.5 pKi 114
pKi 9.5 [114]
atropine Rn Antagonist 9.0 – 9.1 pKi 58,60
pKi 9.0 – 9.1 [58,60]
dexetimide Hs Antagonist 8.9 pKi 60
pKi 8.9 [60]
ipratropium Hs Antagonist 8.8 pKi 47
pKi 8.8 [47]
dexetimide Rn Antagonist 8.8 pKi 60
pKi 8.8 [60]
Alexa-488-telenzepine Hs Antagonist 8.8 pKi 87
pKi 8.8 [87]
scopolamine Hs Antagonist 8.7 pKi 49
pKi 8.7 [49]
SCH 57790 Hs Antagonist 8.6 pKi 62
pKi 8.6 [62]
AE9C90CB Hs Antagonist 8.6 pKi 110
pKi 8.6 [110]
benzatropine Rn Antagonist 8.6 pKi 88
pKi 8.6 (Ki 2.6x10-9 M) [88]
Description: Displacement binding assay using homogenised rat caudate putamen.
atropine Hs Antagonist 7.8 – 9.2 pKi 13,20,47,49,60,86,95
pKi 7.8 – 9.2 [13,20,47,49,60,86,95]
tolterodine Hs Inverse agonist 8.4 – 8.6 pKi 40,86,110
pKi 8.4 – 8.6 [40,86,110]
AQ-RA 741 Hs Antagonist 8.4 pKi 29,40
pKi 8.4 [29,40]
4-DAMP Hs Antagonist 8.3 pKi 60
pKi 8.3 [60]
4-DAMP Rn Antagonist 8.2 pKi 58,60
pKi 8.2 [58,60]
AFDX384 Hs Antagonist 8.2 pKi 29
pKi 8.2 [29]
himbacine Hs Antagonist 7.9 – 8.4 pKi 29,57,60,81
pKi 7.9 – 8.4 [29,57,60,81]
ethopropazine Rn Antagonist 8.1 pKi 14
pKi 8.1 (Ki 7.2x10-9 M) [14]
Description: Displacement of [H]QNB binding in rat hindbrain brain homogenate.
amitriptyline Hs Antagonist 7.9 pKi 112
pKi 7.9 (Ki 1.18x10-8 M) [112]
oxybutynin Hs Inverse agonist 7.9 pKi 26
pKi 7.9 (Ki 1.175x10-8 M) [26]
himbacine Rn Antagonist 7.9 pKi 60
pKi 7.9 [60]
oxybutynin Hs Antagonist 7.7 – 8.1 pKi 50,110
pKi 7.7 – 8.1 [50,110]
methoctramine Hs Antagonist 7.3 – 8.4 pKi 13,29,33,46,60,86
pKi 7.3 – 8.4 [13,29,33,46,60,86]
hexocyclium Hs Antagonist 7.6 pKi 13
pKi 7.6 [13]
silahexocyclium Hs Antagonist 7.5 pKi 13
pKi 7.5 [13]
UH-AH 37 Hs Antagonist 7.3 – 7.4 pKi 40,138
pKi 7.3 – 7.4 [40,138]
darifenacin Hs Inverse agonist 7.0 – 7.6 pKi 40,46-47,50,86,110
pKi 7.0 – 7.6 [40,46-47,50,86,110]
methoctramine Rn Antagonist 7.3 pKi 60
pKi 7.3 [60]
solifenacin Hs Antagonist 6.9 – 7.1 pKi 50,110
pKi 6.9 – 7.1 [50,110]
dosulepin Hs Antagonist 7.0 pKi 112
pKi 7.0 (Ki 1.09x10-7 M) [112]
otenzepad Hs Antagonist 6.7 – 7.2 pKi 13,60
pKi 6.7 – 7.2 [13,60]
imipramine Hs Antagonist 6.9 pKi 60
pKi 6.9 [60]
hexahydrosiladifenidol Rn Antagonist 6.7 – 6.8 pKi 58,60
pKi 6.7 – 6.8 [58,60]
hexahydrosiladifenidol Hs Antagonist 6.6 – 6.8 pKi 13,33,60
pKi 6.6 – 6.8 [13,33,60]
hexahydrodifenidol Hs Antagonist 6.7 pKi 13
pKi 6.7 [13]
dicyclomine Hs Antagonist 6.6 pKi 13
pKi 6.6 [13]
pirenzepine Rn Antagonist 5.3 – 7.4 pKi 58,60,113
pKi 5.3 – 7.4 [58,60,113]
p-F-HHSiD Hs Antagonist 6.1 – 6.6 pKi 33,49
pKi 6.1 – 6.6 [33,49]
pirenzepine Hs Antagonist 6.0 – 6.7 pKi 13,29,46,49,57,60,86,138
pKi 6.0 – 6.7 [13,29,46,49,57,60,86,138]
VU0255035 Hs Antagonist 6.2 pKi 108
pKi 6.2 [108]
muscarinic toxin 3 Hs Antagonist <6.0 pKi 57
pKi <6.0 [57]
otenzepad Rn Antagonist 4.6 – 7.3 pKi 58,60,113
pKi 4.6 – 7.3 [58,60,113]
lithocholylcholine Hs Antagonist 5.4 pKi 20
pKi 5.4 [20]
guanylpirenzepine Rn Antagonist 5.3 pKi 131
pKi 5.3 [131]
muscarinic toxin 7 Hs Antagonist <5.0 pKi 89
pKi <5.0 [89]
levetimide Hs Antagonist 5.0 pKi 60
pKi 5.0 [60]
levetimide Rn Antagonist 4.8 pKi 60
pKi 4.8 [60]
ML381 Hs Antagonist <4.5 pKi 38
pKi <4.5 (Ki >3x10-5 M) [38]
aclidinium Hs Antagonist 9.8 pIC50 97
pIC50 9.8 (IC50 1.7x10-10 M) [97]
glycopyrrolate Hs Full agonist 9.3 pIC50 117
pIC50 9.3 (IC50 5.01x10-10 M) [117]
Description: Assay uses glycopyrronium bromide
solifenacin Hs Antagonist 6.2 pIC50 96
pIC50 6.2 (IC50 5.73x10-7 M) [96]
View species-specific antagonist tables
Antagonist Comments
Dexetimide is the optical isomer of levetimide [60].

Biperiden is an approved drug antagonist of muscarinic acetylcholine receptors. We have tagged the M1 subtype as the drug's primary target as affinity is 10-fold higher at this receptor subtype [8].
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]dimethyl-W84 Hs Positive 8.5 pKd 124
pKd 8.5 [124]
C7/3-phth Hs Negative 7.1 pKd 22
pKd 7.1 [22]
W-84 Hs Negative 6.0 – 7.5 pKd 84,124
pKd 6.0 – 7.5 [84,124]
alcuronium Hs Negative 6.1 – 6.9 pKd 55,124
pKd 6.1 – 6.9 [55,124]
gallamine Hs Negative 5.9 – 6.3 pKd 23,66
pKd 5.9 – 6.3 [23,66]
WIN 51,708 Hs Negative 5.9 pKd 71
pKd 5.9 [71]
KT 5823 Hs Positive 5.7 pKd 70
pKd 5.7 [70]
LY2119620 Hs Positive 5.7 pKd 25,61
pKd 5.7 [25,61]
WIN 62,577 Hs Negative 5.3 pKd 71
pKd 5.3 [71]
staurosporine Hs Positive 5.1 pKd 70
pKd 5.1 [70]
vincamine Hs Neutral 5.1 pKd 55
pKd 5.1 [55]
Gö 7874 Hs Negative 5.0 pKd 70
pKd 5.0 [70]
strychnine Hs Positive 4.9 – 5.0 pKd 55,66,124
pKd 4.9 – 5.0 [55,66,124]
N-benzyl brucine Hs Negative 4.8 pKd 69
pKd 4.8 [69]
N-benzyl brucine Hs Positive 4.8 pKd 69
pKd 4.8 [69]
N-chloromethyl-brucine Hs Negative 4.6 pKd 69
pKd 4.6 [69]
N-chloromethyl-brucine Hs Positive 4.6 pKd 69
pKd 4.6 [69]
brucine Hs Positive 4.3 – 4.6 pKd 55,69
pKd 4.3 – 4.6 [55,69]
LY2033298 Hs Positive 4.4 pKd 128
pKd 4.4 [128]
brucine Hs Negative 4.3 pKd 69
pKd 4.3 [69]
vinburnine Hs Neutral 4.2 pKd 55
pKd 4.2 [55]
thiochrome Hs Neutral 3.9 pKd 67
pKd 3.9 [67]
brucine N-oxide Hs Negative 3.5 pKd 69
pKd 3.5 [69]
brucine N-oxide Hs Positive 3.5 pKd 69
pKd 3.5 [69]
dimethyl-W84 Hs Positive 8.5 pKi 124
pKi 8.5 [124]
W-84 Hs Positive 7.6 pKi 124
pKi 7.6 [124]
WDuo3 Hs Positive 6.9 pKi 124
pKi 6.9 [124]
gallamine Hs Negative 5.8 – 7.6 pKi 60,124
pKi 5.8 – 7.6 [60,124]
gallamine Rn Negative 5.6 pKi 60
pKi 5.6 [60]
Duo3 Hs Positive 7.1 pEC50 123
pEC50 7.1 [123]
tacrine Mm Negative 5.7 pIC50 111
pIC50 5.7 (IC50 2.1x10-6 M) [111]
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