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M1 receptor

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Target not currently curated in GtoImmuPdb

Target id: 13

Nomenclature: M1 receptor

Family: Acetylcholine receptors (muscarinic)

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 460 11q12.3 CHRM1 cholinergic receptor muscarinic 1 12,107
Mouse 7 460 19 A Chrm1 cholinergic receptor, muscarinic 1, CNS 91,122
Rat 7 460 1q43 Chrm1 cholinergic receptor, muscarinic 1 71,105,130,140
Previous and Unofficial Names Click here for help
M1 muscarinic acetylcholine receptor | Chrm-1 | M1R | cholinergic receptor, muscarinic 1 | cholinergic receptor | cholinergic receptor, muscarinic 1, CNS
Database Links Click here for help
Specialist databases
GPCRdb acm1_human (Hs), acm1_mouse (Mm), acm1_rat (Rn)
Other databases
Alphafold P11229 (Hs), P12657 (Mm), P08482 (Rn)
ChEMBL Target CHEMBL216 (Hs), CHEMBL3733 (Mm), CHEMBL276 (Rn)
DrugBank Target P11229 (Hs)
Ensembl Gene ENSG00000168539 (Hs), ENSMUSG00000032773 (Mm), ENSRNOG00000018385 (Rn)
Entrez Gene 1128 (Hs), 12669 (Mm), 25229 (Rn)
Human Protein Atlas ENSG00000168539 (Hs)
KEGG Gene hsa:1128 (Hs), mmu:12669 (Mm), rno:25229 (Rn)
OMIM 118510 (Hs)
Pharos P11229 (Hs)
RefSeq Nucleotide NM_000738 (Hs), NM_007698 (Mm), NM_080773 (Rn)
RefSeq Protein NP_000729 (Hs), NP_031724 (Mm), NP_542951 (Rn)
SynPHARM 82388 (in complex with tiotropium)
UniProtKB P11229 (Hs), P12657 (Mm), P08482 (Rn)
Wikipedia CHRM1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the human M1 muscarinic acetylcholine receptor bound to antagonist tiotropium.
PDB Id:  5CXV
Ligand:  tiotropium
Resolution:  2.7Å
Species:  Human
References:  139
Natural/Endogenous Ligands Click here for help
acetylcholine

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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]iperoxo Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Agonist 8.7 pKd 120
⤷ pKd 8.7 [120]
NNC 11-1585 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 9.9 pKi 26
⤷ pKi 9.9 [26]
NNC 11-1607 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.6 pKi 26
⤷ pKi 8.6 [26]
pentylthio-TZTP Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.6 pKi 64
⤷ pKi 8.6 [64]
NNC 11-1314 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.4 pKi 26
⤷ pKi 7.4 [26]
xanomeline Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 6.7 – 7.9 pKi 27,109,149,161
⤷ pKi 6.7 – 7.9 [27,109,149,161]
sabcomeline Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 6.7 pKi 161
⤷ pKi 6.7 [161]
arecaidine propargyl ester Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.4 pKi 64
⤷ pKi 6.4 [64]
LY593093 Small molecule or natural product Hs Partial agonist 6.2 pKi 151
⤷ pKi 6.2 [151]
AC-42 Small molecule or natural product Hs Full agonist 6.2 pKi 75
⤷ pKi 6.2 [75]
oxotremorine Small molecule or natural product Click here for species-specific activity table Rn Partial agonist 6.0 pKi 93
⤷ pKi 6.0 [93]
arecoline Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.7 pKi 64,103,114
⤷ pKi 5.7 [64,103,114]
oxotremorine-M Small molecule or natural product Rn Full agonist 5.6 pKi 93
⤷ pKi 5.6 [93]
oxotremorine Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 5.5 pKi 64,114
⤷ pKi 5.5 [64,114]
cevimeline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 5.3 pKi 84
⤷ pKi 5.3 (Ki 4.85x10-6 M) [84]
Description: Displacement of [3H]QNB from cloned receptor.
arecoline Small molecule or natural product Rn Partial agonist 5.3 pKi 93
⤷ pKi 5.3 [93]
McN-A-343 Small molecule or natural product Click here for species-specific activity table Rn Partial agonist 5.1 pKi 93
⤷ pKi 5.1 [93]
oxotremorine-M Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.1 pKi 64
⤷ pKi 5.1 [64]
pilocarpine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 5.1 pKi 64,114
⤷ pKi 5.1 [64,114]
McN-A-343 Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 4.8 – 5.2 pKi 114
⤷ pKi 4.8 – 5.2 [114]
acetylcholine 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 5.0 pKi 25
⤷ pKi 5.0 [25]
pilocarpine Small molecule or natural product Approved drug Ligand has a PDB structure Rn Partial agonist 4.9 pKi 93
⤷ pKi 4.9 [93]
milameline Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 4.8 pKi 161
⤷ pKi 4.8 [161]
acetylcholine 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 4.3 – 4.9 pKi 64,68
⤷ pKi 4.3 – 4.9 [64,68]
methylfurmethide Small molecule or natural product Click here for species-specific activity table Hs Full agonist 4.6 pKi 64
⤷ pKi 4.6 [64]
(-)-YM796 Small molecule or natural product Hs Partial agonist 4.3 – 4.8 pKi 152
⤷ pKi 4.3 – 4.8 [152]
(±)YM796 Small molecule or natural product Hs Partial agonist 4.1 – 4.7 pKi 152
⤷ pKi 4.1 – 4.7 [152]
carbachol Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 3.2 – 5.3 pKi 27,64,161
⤷ pKi 3.2 – 5.3 [27,64,161]
furtrethonium Small molecule or natural product Click here for species-specific activity table Hs Full agonist 4.1 pKi 64
⤷ pKi 4.1 [64]
bethanechol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 4.0 pKi 64,114
⤷ pKi 4.0 [64,114]
carbachol Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Full agonist 3.9 pKi 25
⤷ pKi 3.9 [25]
bethanechol Small molecule or natural product Approved drug Rn Full agonist 3.7 pKi 93
⤷ pKi 3.7 [93]
AZD6088 Small molecule or natural product Primary target of this compound Hs Partial agonist 8.3 pEC50 97
⤷ pEC50 8.3 (EC50 5x10-9 M) [97]
methacholine Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Rn Agonist 6.4 pEC50 104,114
⤷ pEC50 6.4 (EC50 4x10-7 M) [104,114]
(+)-aceclidine Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.4 pEC50 35
⤷ pEC50 5.4 [35]
(-)-aceclidine Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 5.0 pEC50 35
⤷ pEC50 5.0 [35]
[11C]butylthio-TZTP Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Full agonist - - 38
⤷ [38]
[11C]xanomeline Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Full agonist - - 38
⤷ [38]
iperoxo Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Agonist - - 120
⤷ [120]
[3H]acetylcholine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Agonist - -
⤷
SPP1 Small molecule or natural product N/A Agonist - - 15
⤷ [15]
View species-specific agonist tables
Agonist Comments
Please consult references [17,79,114,147,158] for further details of the activity of some of the ligands in this list.

Pilocarpine has been found to be a partial agonist [79,114,158] as well as a full agonist [147] at the M1 receptor; oxotremorine has also been found to be a partial agonist [79,114,147] as well as a full agonist [114] at the M1 receptor.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]QNB Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 10.6 – 10.8 pKd 63,107
⤷ pKd 10.6 – 10.8 (Kd 2.51x10-11 – 1.58x10-11 M) [63,107]
Cy3B-telenzepine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Hs Antagonist 10.5 pKd 56
⤷ pKd 10.5 [56]
[3H]N-methyl scopolamine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 9.4 – 10.3 pKd 23,27-28,58,64-66,69,77
⤷ pKd 9.4 – 10.3 (Kd 4.2x10-10 – 5x10-11 M) [23,27-28,58,64-66,69,77]
[3H]N-methyl scopolamine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Rn Antagonist 9.7 pKd 25,147
⤷ pKd 9.7 [25,147]
biperiden Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 9.3 pKd 11
⤷ pKd 9.3 (Kd 4.8x10-10 M) [11]
Alexa-488-telenzepine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Hs Antagonist 9.3 pKd 56
⤷ pKd 9.3 [56]
[3H]darifenacin Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 8.8 pKd 126
⤷ pKd 8.8 [126]
[3H]pirenzepine Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 7.9 pKd 24,119,143,150
⤷ pKd 7.9 (Kd 1.4x10-8 M) [24,119,143,150]
[3H]pirenzepine Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Antagonist 7.7 – 7.9 pKd 37,51
⤷ pKd 7.7 – 7.9 [37,51]
otenzepad Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.2 pKd 36
⤷ pKd 6.2 [36]
tiotropium Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 9.6 – 10.7 pKi 33,111,135,137
⤷ pKi 9.6 – 10.7 [33,111,135,137]
N-methyl scopolamine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 9.9 pKi 40
⤷ pKi 9.9 [40]
umeclidinium Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 9.8 pKi 73,118
⤷ pKi 9.8 (Ki 1.6x10-10 M) [73,118]
propantheline Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 9.7 pKi 60
⤷ pKi 9.7 [60]
ipratropium Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 9.3 – 9.8 pKi 58,111
⤷ pKi 9.3 – 9.8 [58,111]
[3H](+)telenzepine Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Antagonist 9.4 pKi 37
⤷ pKi 9.4 [37]
revefenacin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 9.4 pKi 55
⤷ pKi 9.4 (Ki 4.17x10-10 M) [55]
Description: Determined from a radioligand binding assay using membranes from CHO‐K1 cells expressing the hM1 receptor, and displacement of [3H]NMS tracer.
atropine Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 9.0 – 9.7 pKi 18,25,67
⤷ pKi 9.0 – 9.7 [18,25,67]
4-DAMP Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.3 pKi 34
⤷ pKi 9.3 [34]
dicyclomine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 9.1 pKi 5
⤷ pKi 9.1 (Ki 8.3x10-10 M) [5]
atropine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.5 – 9.6 pKi 27,40,58,60,107,126
⤷ pKi 8.5 – 9.6 [27,40,58,60,107,126]
benzatropine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 9.0 pKi 99
⤷ pKi 9.0 (Ki 9.5x10-10 M) [99]
Description: Displacement binding experiment using homogenised rat caudate putamen.
darifenacin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.9 – 9.1 pKi 45,58,125
⤷ pKi 8.9 – 9.1 [45,58,125]
scopolamine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 9.0 pKi 30,60
⤷ pKi 9.0 [30,60]
4-DAMP Small molecule or natural product Click here for species-specific activity table Rn Antagonist 8.9 pKi 67
⤷ pKi 8.9 [67]
trihexyphenidyl Small molecule or natural product Approved drug Primary target of this compound Hs Antagonist 8.9 pKi 5
⤷ pKi 8.9 (Ki 1.35x10-9 M) [5]
tripitramine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.8 pKi 87
⤷ pKi 8.8 [87]
silahexocyclium Small molecule or natural product Rn Antagonist 8.7 pKi 18
⤷ pKi 8.7 [18]
hexocyclium Small molecule or natural product Rn Antagonist 8.6 pKi 18
⤷ pKi 8.6 [18]
oxybutynin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.6 pKi 32,125
⤷ pKi 8.6 (Ki 2.4x10-9 M) [32,125]
ethopropazine Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 8.5 pKi 19
⤷ pKi 8.5 (Ki 3.1x10-9 M) [19]
Description: Displacement of [H]QNB binding in rat forebrain brain homogenate.
tolterodine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.4 – 8.5 pKi 45,125
⤷ pKi 8.4 – 8.5 [45,125]
oxybutynin Small molecule or natural product Approved drug Rn Antagonist 8.2 pKi 98
⤷ pKi 8.2 [98]
hexahydrodifenidol Small molecule or natural product Rn Antagonist 8.0 pKi 18
⤷ pKi 8.0 [18]
solifenacin Small molecule or natural product Approved drug Rn Antagonist 8.0 pKi 98
⤷ pKi 8.0 [98]
pirenzepine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.6 – 8.3 pKi 18,34,54,60,66,157
⤷ pKi 7.6 – 8.3 [18,34,54,60,66,157]
pirenzepine Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 7.8 – 7.9 pKi 18,67
⤷ pKi 7.8 – 7.9 [18,67]
amitriptyline Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.8 pKi 129
⤷ pKi 7.8 (Ki 1.47x10-8 M) [129]
methoctramine Small molecule or natural product Click here for species-specific activity table Rn Antagonist 7.8 pKi 18
⤷ pKi 7.8 [18]
VU0255035 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.8 pKi 123
⤷ pKi 7.8 (Ki 1.487x10-8 M) [123]
dosulepin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.7 pKi 129
⤷ pKi 7.7 (Ki 1.8x10-8 M) [129]
hexahydrosiladifenidol Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.7 pKi 36
⤷ pKi 7.7 [36]
hexahydrosiladifenidol Small molecule or natural product Click here for species-specific activity table Rn Antagonist 7.4 – 7.9 pKi 18,67
⤷ pKi 7.4 – 7.9 [18,67]
solifenacin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.6 pKi 61,125
⤷ pKi 7.6 [61,125]
AFDX384 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.5 pKi 34
⤷ pKi 7.5 [34]
p-F-HHSiD Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.1 – 7.8 pKi 36,60
⤷ pKi 7.1 – 7.8 [36,60]
muscarinic toxin 1 Peptide Click here for species-specific activity table Hs Antagonist 7.3 – 7.6 pKi 40,52
⤷ pKi 7.3 – 7.6 [40,52]
guanylpirenzepine Small molecule or natural product Click here for species-specific activity table Rn Antagonist 7.3 – 7.6 pKi 3,146
⤷ pKi 7.3 – 7.6 [3,146]
AQ-RA 741 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.2 – 7.5 pKi 34,45
⤷ pKi 7.2 – 7.5 [34,45]
muscarinic toxin 3 Peptide Click here for species-specific activity table Hs Antagonist 7.1 pKi 66
⤷ pKi 7.1 [66]
droxidopa Small molecule or natural product Approved drug Hs Antagonist 7.1 pKi 30
⤷ pKi 7.1 [30]
BODIPY-pirenzepine Small molecule or natural product Ligand is labelled Hs Antagonist 7.0 pKi 62
⤷ pKi 7.0 [62]
methoctramine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.6 – 7.3 pKi 34,36,54,126
⤷ pKi 6.6 – 7.3 [34,36,54,126]
himbacine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.7 – 7.1 pKi 34,66,95
⤷ pKi 6.7 – 7.1 [34,66,95]
(S)-dimetindene Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 6.7 pKi 21
⤷ pKi 6.7 (Ki 1.906x10-7 M) [21]
Description: Binding to hM1 receptors expressed in CHO cells.
muscarinic toxin 2 Peptide Click here for species-specific activity table Hs Antagonist 6.4 pKi 52
⤷ pKi 6.4 [52]
otenzepad Small molecule or natural product Click here for species-specific activity table Rn Antagonist 5.9 – 6.3 pKi 18,67
⤷ pKi 5.9 – 6.3 [18,67]
lithocholylcholine Small molecule or natural product Click here for species-specific activity table Rn Antagonist 5.6 pKi 25
⤷ pKi 5.6 [25]
ML381 Small molecule or natural product Click here for species-specific activity table Hs Antagonist <5.0 pKi 42
⤷ pKi <5.0 (Ki >1x10-5 M) [42]
aclidinium Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 10.1 – 10.2 pIC50 111,137
⤷ pIC50 10.1 – 10.2 [111,137]
glycopyrrolate Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 9.6 – 10.1 pIC50 131,135
⤷ pIC50 9.6 – 10.1 [131,135]
Description: Assay uses glycopyrronium bromide
solifenacin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.2 pIC50 110
⤷ pIC50 7.2 (IC50 6.35x10-8 M) [110]
[18F](R,R)-quinuclidinyl-4-fluoromethyl-benzilate Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Antagonist - - 70
⤷ [70]
View species-specific antagonist tables
Antagonist Comments
Recombinant MT7 (rMT7) is often used for bioassays due to the limited availability of the M1 muscarinic receptor-selective mamba toxin MT7 or m1-toxin 1 (rMT7 has comparable affinity for M1 [100]).

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 [11]. Ethopropazine appears to have highest affinity for the M1 subtype in rat brain homegenates [19], so the M1 receptor is the likely primary human target of this drug.
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
benzoquinazolinone 12 Small molecule or natural product Hs Positive 6.6 pKB 1
⤷ pKB 6.6 [1]
BQCA Small molecule or natural product Hs Positive 4.0 – 4.8 pKB 1-2,22,86
⤷ pKB 4.0 – 4.8 [1-2,22,86]
KT 5720 Small molecule or natural product Click here for species-specific activity table Hs Positive 6.4 pKd 81
⤷ pKd 6.4 (Kd 3.98x10-7 M) [81]
staurosporine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Positive 5.9 pKd 81
⤷ pKd 5.9 [81]
Gö 7874 Small molecule or natural product Click here for species-specific activity table Hs Negative 5.8 pKd 81
⤷ pKd 5.8 [81]
WIN 51,708 Small molecule or natural product Click here for species-specific activity table Hs Negative 5.8 pKd 82
⤷ pKd 5.8 [82]
KT 5823 Small molecule or natural product Click here for species-specific activity table Hs Positive 5.7 pKd 81
⤷ pKd 5.7 [81]
WIN 62,577 Small molecule or natural product Click here for species-specific activity table