M<sub>1</sub> receptor | Acetylcholine receptors (muscarinic) | IUPHAR/BPS Guide to PHARMACOLOGY

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M1 receptor

Target not currently curated in GtoImmuPdb

Target id: 13

Nomenclature: M1 receptor

Family: Acetylcholine receptors (muscarinic)

Contents:

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 460 11q13 CHRM1 cholinergic receptor muscarinic 1 12,101
Mouse 7 460 19 A Chrm1 cholinergic receptor, muscarinic 1, CNS 87,111
Rat 7 460 1q43-q51 Chrm1 cholinergic receptor, muscarinic 1 67,99,119,127
Previous and Unofficial Names
M1 muscarinic acetylcholine receptor | Chrm-1 | M1R | cholinergic receptor, muscarinic 1 | cholinergic receptor | cholinergic receptor, muscarinic 1, CNS
Database Links
Specialist databases
GPCRDB acm1_human (Hs), acm1_mouse (Mm), acm1_rat (Rn)
Other databases
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
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:  126
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 Value Parameter Reference
NNC 11-1585 Hs Full agonist 9.9 pKi 25
⤷ pKi 9.9 [25]
NNC 11-1607 Hs Full agonist 8.6 pKi 25
⤷ pKi 8.6 [25]
pentylthio-TZTP Hs Full agonist 8.6 pKi 61
⤷ pKi 8.6 [61]
NNC 11-1314 Hs Full agonist 7.4 pKi 25
⤷ pKi 7.4 [25]
xanomeline Hs Partial agonist 6.7 – 7.9 pKi 26,62,134,146
⤷ pKi 6.7 – 7.9 [26,62,134,146]
sabcomeline Hs Partial agonist 6.7 pKi 146
⤷ pKi 6.7 [146]
arecaidine propargyl ester Hs Full agonist 6.4 pKi 61
⤷ pKi 6.4 [61]
LY593093 Hs Partial agonist 6.2 pKi 136
⤷ pKi 6.2 [136]
AC-42 Hs Full agonist 6.2 pKi 71
⤷ pKi 6.2 [71]
oxotremorine Rn Partial agonist 6.0 pKi 89
⤷ pKi 6.0 [89]
arecoline Hs Full agonist 5.7 pKi 61
⤷ pKi 5.7 [61]
oxotremorine-M Rn Full agonist 5.6 pKi 89
⤷ pKi 5.6 [89]
oxotremorine Hs Partial agonist 5.5 pKi 61
⤷ pKi 5.5 [61]
cevimeline Hs Agonist 5.3 pKi 80
⤷ pKi 5.3 (Ki 4.85x10-6 M) [80]
Description: Displacement of [3H]QNB from cloned receptor.
arecoline Rn Partial agonist 5.3 pKi 89
⤷ pKi 5.3 [89]
McN-A-343 Rn Partial agonist 5.1 pKi 89
⤷ pKi 5.1 [89]
oxotremorine-M Hs Full agonist 5.1 pKi 61
⤷ pKi 5.1 [61]
pilocarpine Hs Partial agonist 5.1 pKi 61
⤷ pKi 5.1 [61]
McN-A-343 Hs Partial agonist 4.8 – 5.2 pKi 106
⤷ pKi 4.8 – 5.2 [106]
acetylcholine Rn Full agonist 5.0 pKi 24
⤷ pKi 5.0 [24]
pilocarpine Rn Partial agonist 4.9 pKi 89
⤷ pKi 4.9 [89]
milameline Hs Partial agonist 4.8 pKi 146
⤷ pKi 4.8 [146]
acetylcholine Hs Full agonist 4.3 – 4.9 pKi 61,73
⤷ pKi 4.3 – 4.9 [61,73]
methylfurmethide Hs Full agonist 4.6 pKi 61
⤷ pKi 4.6 [61]
(-)-YM796 Hs Partial agonist 4.3 – 4.8 pKi 137
⤷ pKi 4.3 – 4.8 [137]
(±)YM796 Hs Partial agonist 4.1 – 4.7 pKi 137
⤷ pKi 4.1 – 4.7 [137]
carbachol Hs Full agonist 3.2 – 5.3 pKi 26,61,146
⤷ pKi 3.2 – 5.3 [26,61,146]
furtrethonium Hs Full agonist 4.1 pKi 61
⤷ pKi 4.1 [61]
bethanechol Hs Full agonist 4.0 pKi 61
⤷ pKi 4.0 [61]
carbachol Rn Full agonist 3.9 pKi 24
⤷ pKi 3.9 [24]
bethanechol Rn Full agonist 3.7 pKi 89
⤷ pKi 3.7 [89]
AZD6088 Hs Partial agonist 8.3 pEC50 93
⤷ pEC50 8.3 (EC50 5x10-9 M) [93]
methacholine Rn Agonist 6.4 pEC50 98
⤷ pEC50 6.4 (EC50 4x10-7 M) [98]
(+)-aceclidine Hs Full agonist 5.4 pEC50 33
⤷ pEC50 5.4 [33]
(-)-aceclidine Hs Partial agonist 5.0 pEC50 33
⤷ pEC50 5.0 [33]
[11C]butylthio-TZTP Hs Full agonist - - 36
⤷ [36]
[11C]xanomeline Hs Full agonist - - 36
⤷ [36]
SPP1 N/A Agonist - - 15
⤷ [15]
View species-specific agonist tables
Agonist Comments
Please consult references [17,75,106,132,143] for further details of the activity of some of the ligands in this list.

Pilocarpine has been found to be a partial agonist [75,106,143] as well as a full agonist [132] at the M1 receptor; oxotremorine has also been found to be a partial agonist [75,106,132] as well as a full agonist [106] 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 Hs Antagonist 10.6 – 10.8 pKd 27,101
⤷ pKd 10.6 – 10.8 (Kd 2.51x10-11 – 1.58x10-11 M) [27,101]
Cy3B-telenzepine Hs Antagonist 10.5 pKd 54
⤷ pKd 10.5 [54]
[3H]N-methyl scopolamine Hs Antagonist 9.4 – 10.3 pKd 23,26-27,56,61-63,65,73
⤷ pKd 9.4 – 10.3 (Kd 4.2x10-10 – 5x10-11 M) [23,26-27,56,61-63,65,73]
[3H]N-methyl scopolamine Rn Antagonist 9.7 pKd 24,132
⤷ pKd 9.7 [24,132]
biperiden Hs Antagonist 9.3 pKd 11
⤷ pKd 9.3 (Kd 4.8x10-10 M) [11]
Alexa-488-telenzepine Hs Antagonist 9.3 pKd 54
⤷ pKd 9.3 [54]
[3H]darifenacin Hs Antagonist 8.8 pKd 115
⤷ pKd 8.8 [115]
[3H]pirenzepine Hs Antagonist 7.9 pKd 135
⤷ pKd 7.9 (Kd 1.4x10-8 M) [135]
[3H]pirenzepine Rn Antagonist 7.7 – 7.9 pKd 35,49
⤷ pKd 7.7 – 7.9 [35,49]
otenzepad Hs Antagonist 6.2 pKd 34
⤷ pKd 6.2 [34]
N-methyl scopolamine Hs Antagonist 9.9 pKi 38
⤷ pKi 9.9 [38]
umeclidinium Hs Antagonist 9.8 pKi 69,109
⤷ pKi 9.8 (Ki 1.6x10-10 M) [69,109]
propantheline Hs Antagonist 9.7 pKi 58
⤷ pKi 9.7 [58]
AE9C90CB Hs Antagonist 9.7 pKi 114
⤷ pKi 9.7 [114]
tiotropium Hs Antagonist 9.6 pKi 31
⤷ pKi 9.6 [31]
[3H](+)telenzepine Rn Antagonist 9.4 pKi 35
⤷ pKi 9.4 [35]
revefenacin Hs Antagonist 9.4 pKi 53
⤷ pKi 9.4 (Ki 4.17x10-10 M) [53]
Description: Determined from a radioligand binding assay using membranes from CHO‐K1 cells expressing the hM1 receptor, and displacement of [3H]NMS tracer.
atropine Rn Antagonist 9.0 – 9.7 pKi 18,24,64
⤷ pKi 9.0 – 9.7 [18,24,64]
ipratropium Hs Antagonist 9.3 pKi 56
⤷ pKi 9.3 [56]
4-DAMP Hs Antagonist 9.2 pKi 32
⤷ pKi 9.2 [32]
dicyclomine Hs Antagonist 9.1 pKi 5
⤷ pKi 9.1 (Ki 8.3x10-10 M) [5]
atropine Hs Antagonist 8.5 – 9.6 pKi 26,38,56,58,101,115
⤷ pKi 8.5 – 9.6 [26,38,56,58,101,115]
benzatropine Rn Antagonist 9.0 pKi 95
⤷ pKi 9.0 (Ki 9.5x10-10 M) [95]
Description: Displacement binding experiment using homogenised rat caudate putamen.
scopolamine Hs Antagonist 9.0 pKi 58
⤷ pKi 9.0 [58]
4-DAMP Rn Antagonist 8.9 pKi 64
⤷ pKi 8.9 [64]
trihexyphenidyl Hs Antagonist 8.9 pKi 5
⤷ pKi 8.9 (Ki 1.35x10-9 M) [5]
tripitramine Hs Antagonist 8.8 pKi 83
⤷ pKi 8.8 [83]
silahexocyclium Rn Antagonist 8.7 pKi 18
⤷ pKi 8.7 [18]
UH-AH 37 Hs Antagonist 8.6 – 8.7 pKi 43,142
⤷ pKi 8.6 – 8.7 [43,142]
hexocyclium Rn Antagonist 8.6 pKi 18
⤷ pKi 8.6 [18]
oxybutynin Hs Antagonist 8.6 pKi 30,59,114
⤷ pKi 8.6 (Ki 2.4x10-9 M) [30,59,114]
tolterodine Hs Antagonist 8.5 – 8.7 pKi 43,114
⤷ pKi 8.5 – 8.7 [43,114]
ethopropazine 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.
oxybutynin Rn Antagonist 8.2 pKi 94
⤷ pKi 8.2 [94]
pirenzepine Hs Antagonist 7.8 – 8.3 pKi 18,32,52,58,63,142
⤷ pKi 7.8 – 8.3 [18,32,52,58,63,142]
hexahydrodifenidol Rn Antagonist 8.0 pKi 18
⤷ pKi 8.0 [18]
solifenacin Rn Antagonist 8.0 pKi 94
⤷ pKi 8.0 [94]
darifenacin Hs Antagonist 7.5 – 8.3 pKi 43,52,56,59,114
⤷ pKi 7.5 – 8.3 [43,52,56,59,114]
pirenzepine Rn Antagonist 7.8 – 7.9 pKi 18,64
⤷ pKi 7.8 – 7.9 [18,64]
amitriptyline Hs Antagonist 7.8 pKi 118
⤷ pKi 7.8 (Ki 1.47x10-8 M) [118]
methoctramine Rn Antagonist 7.8 pKi 18
⤷ pKi 7.8 [18]
VU0255035 Hs Antagonist 7.8 pKi 112
⤷ pKi 7.8 (Ki 1.487x10-8 M) [112]
dosulepin Hs Antagonist 7.7 pKi 118
⤷ pKi 7.7 (Ki 1.8x10-8 M) [118]
hexahydrosiladifenidol Hs Antagonist 7.7 pKi 34
⤷ pKi 7.7 [34]
hexahydrosiladifenidol Rn Antagonist 7.4 – 7.9 pKi 18,64
⤷ pKi 7.4 – 7.9 [18,64]
solifenacin Hs Antagonist 7.6 pKi 59,114
⤷ pKi 7.6 [59,114]
AFDX384 Hs Antagonist 7.5 pKi 32
⤷ pKi 7.5 [32]
p-F-HHSiD Hs Antagonist 7.1 – 7.8 pKi 34,58
⤷ pKi 7.1 – 7.8 [34,58]
muscarinic toxin 1 Hs Antagonist 7.3 – 7.6 pKi 38,50
⤷ pKi 7.3 – 7.6 [38,50]
guanylpirenzepine Rn Antagonist 7.3 – 7.6 pKi 3,131
⤷ pKi 7.3 – 7.6 [3,131]
AQ-RA 741 Hs Antagonist 7.2 – 7.5 pKi 32,43
⤷ pKi 7.2 – 7.5 [32,43]
muscarinic toxin 3 Hs Antagonist 7.1 pKi 63
⤷ pKi 7.1 [63]
BODIPY-pirenzepine Hs Antagonist 7.0 pKi 60
⤷ pKi 7.0 [60]
methoctramine Hs Antagonist 6.6 – 7.3 pKi 32,34,52,115
⤷ pKi 6.6 – 7.3 [32,34,52,115]
himbacine Hs Antagonist 6.7 – 7.1 pKi 32,63,91
⤷ pKi 6.7 – 7.1 [32,63,91]
(S)-dimetindene 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 Hs Antagonist 6.4 pKi 50
⤷ pKi 6.4 [50]
otenzepad Rn Antagonist 5.9 – 6.3 pKi 18,64
⤷ pKi 5.9 – 6.3 [18,64]
lithocholylcholine Rn Antagonist 5.6 pKi 24
⤷ pKi 5.6 [24]
ML381 Hs Antagonist <5.0 pKi 40
⤷ pKi <5.0 (Ki >1x10-5 M) [40]
glycopyrrolate Hs Antagonist 9.9 pIC50 120
⤷ pIC50 9.9 (IC50 1.26x10-10 M) [120]
Description: Assay uses glycopyrronium bromide
aclidinium Hs Antagonist 9.9 pIC50 104
⤷ pIC50 9.9 (IC50 1.4x10-10 M) [104]
Description: Human M1 receptors expressed in CHO-K1 cells
solifenacin Hs Antagonist 7.2 pIC50 103
⤷ pIC50 7.2 (IC50 6.35x10-8 M) [103]
[18F](R,R)-quinuclidinyl-4-fluoromethyl-benzilate Rn Antagonist - - 66
⤷ [66]
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 [96]).

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 Hs Positive 6.6 pKB 1
⤷ pKB 6.6 [1]
BQCA Hs Positive 4.0 – 4.8 pKB 1-2,22,82
⤷ pKB 4.0 – 4.8 [1-2,22,82]
KT 5720 Hs Positive 6.4 pKd 77
⤷ pKd 6.4 (Kd 3.98x10-7 M) [77]
staurosporine Hs Positive 5.9 pKd 77
⤷ pKd 5.9 [77]
Gö 7874 Hs Negative 5.8 pKd 77
⤷ pKd 5.8 [77]
WIN 51,708 Hs Negative 5.8 pKd 78
⤷ pKd 5.8 [78]
KT 5823 Hs Positive 5.7 pKd 77
⤷ pKd 5.7 [77]
WIN 62,577 Hs Negative 5.5 pKd 78
⤷ pKd 5.5 [78]
brucine Hs Positive 4.5 – 5.8 pKd 61,76
⤷ pKd 4.5 – 5.8 (Kd 3x10-5 – 1.78x10-6 M) [61,76]
K-252a Hs Positive 5.1 pKd 77
⤷ pKd 5.1 [77]
vinburnine Hs Neutral 5.1 pKd 61
⤷ pKd 5.1 [61]
alcuronium Hs Negative 5.0 pKd 61
⤷ pKd 5.0 [61]
strychnine Hs Neutral 4.9 – 5.0 pKd 61,73
⤷ pKd 4.9 – 5.0 [61,73]
strychnine