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)

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

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 11,98
Mouse 7 460 19 A Chrm1 cholinergic receptor 84,108
Rat 7 460 1q43-q51 Chrm1 cholinergic receptor 65,96,116,124
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 61 (Hs), 11780 (Mm), 10647 (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)
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:  123
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 Parameter Reference
NNC 11-1585 Hs Full agonist 9.9 pKi 23
pKi 9.9 [23]
NNC 11-1607 Hs Full agonist 8.6 pKi 23
pKi 8.6 [23]
pentylthio-TZTP Hs Full agonist 8.6 pKi 59
pKi 8.6 [59]
NNC 11-1314 Hs Full agonist 7.4 pKi 23
pKi 7.4 [23]
xanomeline Hs Partial agonist 6.7 – 7.9 pKi 24,60,131,143
pKi 6.7 – 7.9 [24,60,131,143]
sabcomeline Hs Partial agonist 6.7 pKi 143
pKi 6.7 [143]
arecaidine propargyl ester Hs Full agonist 6.4 pKi 59
pKi 6.4 [59]
LY593093 Hs Partial agonist 6.2 pKi 133
pKi 6.2 [133]
AC-42 Hs Full agonist 6.2 pKi 69
pKi 6.2 [69]
oxotremorine Rn Partial agonist 6.0 pKi 86
pKi 6.0 [86]
arecoline Hs Full agonist 5.7 pKi 59
pKi 5.7 [59]
oxotremorine-M Rn Full agonist 5.6 pKi 86
pKi 5.6 [86]
oxotremorine Hs Partial agonist 5.5 pKi 59
pKi 5.5 [59]
cevimeline Hs Agonist 5.3 pKi 78
pKi 5.3 (Ki 4.85x10-6 M) [78]
Description: Displacement of [3H]QNB from cloned receptor.
arecoline Rn Partial agonist 5.3 pKi 86
pKi 5.3 [86]
McN-A-343 Rn Partial agonist 5.1 pKi 86
pKi 5.1 [86]
oxotremorine-M Hs Full agonist 5.1 pKi 59
pKi 5.1 [59]
pilocarpine Hs Partial agonist 5.1 pKi 59
pKi 5.1 [59]
McN-A-343 Hs Partial agonist 4.8 – 5.2 pKi 103
pKi 4.8 – 5.2 [103]
acetylcholine Rn Full agonist 5.0 pKi 22
pKi 5.0 [22]
pilocarpine Rn Partial agonist 4.9 pKi 86
pKi 4.9 [86]
milameline Hs Partial agonist 4.8 pKi 143
pKi 4.8 [143]
acetylcholine Hs Full agonist 4.3 – 4.9 pKi 59,71
pKi 4.3 – 4.9 [59,71]
methylfurmethide Hs Full agonist 4.6 pKi 59
pKi 4.6 [59]
(-)-YM796 Hs Partial agonist 4.3 – 4.8 pKi 134
pKi 4.3 – 4.8 [134]
(±)YM796 Hs Partial agonist 4.1 – 4.7 pKi 134
pKi 4.1 – 4.7 [134]
carbachol Hs Full agonist 3.2 – 5.3 pKi 24,59,143
pKi 3.2 – 5.3 [24,59,143]
furtrethonium Hs Full agonist 4.1 pKi 59
pKi 4.1 [59]
bethanechol Hs Full agonist 4.0 pKi 59
pKi 4.0 [59]
carbachol Rn Full agonist 3.9 pKi 22
pKi 3.9 [22]
bethanechol Rn Full agonist 3.7 pKi 86
pKi 3.7 [86]
AZD6088 Hs Partial agonist 8.3 pEC50 90
pEC50 8.3 (EC50 5x10-9 M) [90]
methacholine Rn Agonist 6.4 pEC50 95
pEC50 6.4 (EC50 4x10-7 M) [95]
(+)-aceclidine Hs Full agonist 5.4 pEC50 31
pEC50 5.4 [31]
(-)-aceclidine Hs Partial agonist 5.0 pEC50 31
pEC50 5.0 [31]
[11C]butylthio-TZTP Hs Full agonist - - 34
[34]
[11C]xanomeline Hs Full agonist - - 34
[34]
View species-specific agonist tables
Agonist Comments
Please consult references [15,73,103,129,140] for further details of the activity of some of the ligands in this list.

Pilocarpine has been found to be a partial agonist [73,103,140] as well as a full agonist [129] at the M1 receptor; oxotremorine has also been found to be a partial agonist [73,103,129] as well as a full agonist [103] at the M1 receptor.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Parameter Reference
[3H]QNB Hs Antagonist 10.6 – 10.8 pKd 25,98
pKd 10.6 – 10.8 (Kd 2.51x10-11 – 1.58x10-11 M) [25,98]
Cy3B-telenzepine Hs Antagonist 10.5 pKd 52
pKd 10.5 [52]
[3H]N-methyl scopolamine Hs Antagonist 9.4 – 10.3 pKd 21,24-25,54,59-61,63,71
pKd 9.4 – 10.3 (Kd 4.2x10-10 – 5x10-11 M) [21,24-25,54,59-61,63,71]
[3H]N-methyl scopolamine Rn Antagonist 9.7 pKd 22,129
pKd 9.7 [22,129]
biperiden Hs Antagonist 9.3 pKd 10
pKd 9.3 (Kd 4.8x10-10 M) [10]
Alexa-488-telenzepine Hs Antagonist 9.3 pKd 52
pKd 9.3 [52]
[3H]darifenacin Hs Antagonist 8.8 pKd 112
pKd 8.8 [112]
[3H]pirenzepine Hs Antagonist 7.9 pKd 132
pKd 7.9 (Kd 1.4x10-8 M) [132]
[3H]pirenzepine Rn Antagonist 7.7 – 7.9 pKd 33,47
pKd 7.7 – 7.9 [33,47]
otenzepad Hs Antagonist 6.2 pKd 32
pKd 6.2 [32]
N-methyl scopolamine Hs Antagonist 9.9 pKi 36
pKi 9.9 [36]
umeclidinium Hs Antagonist 9.8 pKi 67,106
pKi 9.8 (Ki 1.6x10-10 M) [67,106]
propantheline Hs Antagonist 9.7 pKi 56
pKi 9.7 [56]
AE9C90CB Hs Antagonist 9.7 pKi 111
pKi 9.7 [111]
tiotropium Hs Antagonist 9.6 pKi 29
pKi 9.6 [29]
[3H](+)telenzepine Rn Antagonist 9.4 pKi 33
pKi 9.4 [33]
revefenacin Hs Antagonist 9.4 pKi 51
pKi 9.4 (Ki 4.17x10-10 M) [51]
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 16,22,62
pKi 9.0 – 9.7 [16,22,62]
ipratropium Hs Antagonist 9.3 pKi 54
pKi 9.3 [54]
4-DAMP Hs Antagonist 9.2 pKi 30
pKi 9.2 [30]
dicyclomine Hs Antagonist 9.1 pKi 5
pKi 9.1 (Ki 8.3x10-10 M) [5]
atropine Hs Antagonist 8.5 – 9.6 pKi 24,36,54,56,98,112
pKi 8.5 – 9.6 [24,36,54,56,98,112]
benzatropine Rn Antagonist 9.0 pKi 92
pKi 9.0 (Ki 9.5x10-10 M) [92]
Description: Displacement binding experiment using homogenised rat caudate putamen.
scopolamine Hs Antagonist 9.0 pKi 56
pKi 9.0 [56]
4-DAMP Rn Antagonist 8.9 pKi 62
pKi 8.9 [62]
trihexyphenidyl Hs Antagonist 8.9 pKi 5
pKi 8.9 (Ki 1.35x10-9 M) [5]
tripitramine Hs Antagonist 8.8 pKi 81
pKi 8.8 [81]
silahexocyclium Rn Antagonist 8.7 pKi 16
pKi 8.7 [16]
UH-AH 37 Hs Antagonist 8.6 – 8.7 pKi 41,139
pKi 8.6 – 8.7 [41,139]
hexocyclium Rn Antagonist 8.6 pKi 16
pKi 8.6 [16]
oxybutynin Hs Antagonist 8.6 pKi 28,57,111
pKi 8.6 (Ki 2.4x10-9 M) [28,57,111]
tolterodine Hs Antagonist 8.5 – 8.7 pKi 41,111
pKi 8.5 – 8.7 [41,111]
ethopropazine Rn Antagonist 8.5 pKi 17
pKi 8.5 (Ki 3.1x10-9 M) [17]
Description: Displacement of [H]QNB binding in rat forebrain brain homogenate.
oxybutynin Rn Antagonist 8.2 pKi 91
pKi 8.2 [91]
pirenzepine Hs Antagonist 7.8 – 8.3 pKi 16,30,50,56,61,139
pKi 7.8 – 8.3 [16,30,50,56,61,139]
hexahydrodifenidol Rn Antagonist 8.0 pKi 16
pKi 8.0 [16]
solifenacin Rn Antagonist 8.0 pKi 91
pKi 8.0 [91]
darifenacin Hs Antagonist 7.5 – 8.3 pKi 41,50,54,57,111
pKi 7.5 – 8.3 [41,50,54,57,111]
pirenzepine Rn Antagonist 7.8 – 7.9 pKi 16,62
pKi 7.8 – 7.9 [16,62]
amitriptyline Hs Antagonist 7.8 pKi 115
pKi 7.8 (Ki 1.47x10-8 M) [115]
methoctramine Rn Antagonist 7.8 pKi 16
pKi 7.8 [16]
VU0255035 Hs Antagonist 7.8 pKi 109
pKi 7.8 (Ki 1.487x10-8 M) [109]
dosulepin Hs Antagonist 7.7 pKi 115
pKi 7.7 (Ki 1.8x10-8 M) [115]
hexahydrosiladifenidol Hs Antagonist 7.7 pKi 32
pKi 7.7 [32]
hexahydrosiladifenidol Rn Antagonist 7.4 – 7.9 pKi 16,62
pKi 7.4 – 7.9 [16,62]
solifenacin Hs Antagonist 7.6 pKi 57,111
pKi 7.6 [57,111]
AFDX384 Hs Antagonist 7.5 pKi 30
pKi 7.5 [30]
p-F-HHSiD Hs Antagonist 7.1 – 7.8 pKi 32,56
pKi 7.1 – 7.8 [32,56]
muscarinic toxin 1 Hs Antagonist 7.3 – 7.6 pKi 36,48
pKi 7.3 – 7.6 [36,48]
guanylpirenzepine Rn Antagonist 7.3 – 7.6 pKi 3,128
pKi 7.3 – 7.6 [3,128]
AQ-RA 741 Hs Antagonist 7.2 – 7.5 pKi 30,41
pKi 7.2 – 7.5 [30,41]
muscarinic toxin 3 Hs Antagonist 7.1 pKi 61
pKi 7.1 [61]
BODIPY-pirenzepine Hs Antagonist 7.0 pKi 58
pKi 7.0 [58]
methoctramine Hs Antagonist 6.6 – 7.3 pKi 30,32,50,112
pKi 6.6 – 7.3 [30,32,50,112]
himbacine Hs Antagonist 6.7 – 7.1 pKi 30,61,88
pKi 6.7 – 7.1 [30,61,88]
(S)-dimetindene Hs Antagonist 6.7 pKi 19
pKi 6.7 (Ki 1.906x10-7 M) [19]
Description: Binding to hM1 receptors expressed in CHO cells.
muscarinic toxin 2 Hs Antagonist 6.4 pKi 48
pKi 6.4 [48]
otenzepad Rn Antagonist 5.9 – 6.3 pKi 16,62
pKi 5.9 – 6.3 [16,62]
lithocholylcholine Rn Antagonist 5.6 pKi 22
pKi 5.6 [22]
ML381 Hs Antagonist <5.0 pKi 38
pKi <5.0 (Ki >1x10-5 M) [38]
glycopyrrolate Hs Antagonist 9.9 pIC50 117
pIC50 9.9 (IC50 1.26x10-10 M) [117]
Description: Assay uses glycopyrronium bromide
aclidinium Hs Antagonist 9.9 pIC50 101
pIC50 9.9 (IC50 1.4x10-10 M) [101]
Description: Human M1 receptors expressed in CHO-K1 cells
solifenacin Hs Antagonist 7.2 pIC50 100
pIC50 7.2 (IC50 6.35x10-8 M) [100]
[18F](R,R)-quinuclidinyl-4-fluoromethyl-benzilate Rn Antagonist - - 64
[64]
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 [93]).

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 [10]. Ethopropazine appears to have highest affinity for the M1 subtype in rat brain homegenates [17], 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 Affinity Parameter Reference
benzoquinazolinone 12 Hs Positive 6.6 pKB 1
pKB 6.6 [1]
BQCA Hs Positive 4.0 – 4.8 pKB 1-2,20,80
pKB 4.0 – 4.8 [1-2,20,80]
KT 5720 Hs Positive 6.4 pKd 75
pKd 6.4 (Kd 3.98x10-7 M) [75]
staurosporine Hs Positive 5.9 pKd 75
pKd 5.9 [75]
Gö 7874 Hs Negative 5.8 pKd 75
pKd 5.8 [75]
WIN 51,708 Hs Negative 5.8 pKd 76
pKd 5.8 [76]
KT 5823 Hs Positive 5.7 pKd 75
pKd 5.7 [75]
WIN 62,577 Hs Negative 5.5 pKd 76
pKd 5.5 [76]
brucine Hs Positive 4.5 – 5.8 pKd 59,74
pKd 4.5 – 5.8 (Kd 3x10-5 – 1.78x10-6 M) [59,74]
K-252a Hs Positive 5.1 pKd 75
pKd 5.1 [75]
vinburnine Hs Neutral 5.1 pKd 59
pKd 5.1 [59]
alcuronium Hs Negative 5.0 pKd 59
pKd 5.0 [59]
strychnine Hs Neutral 4.9 – 5.0 pKd 59,71
pKd 4.9 – 5.0 [59,71]
strychnine Hs Negative 4.9 pKd 71
pKd 4.9 [71]
vincamine Hs Neutral 4.8 pKd 59
pKd 4.8 [59]
brucine Hs Neutral 4.5 pKd 74
pKd 4.5 [74]
N-benzyl brucine Hs Negative 4.4 pKd 74
pKd 4.4 [74]
N-chloromethyl-brucine Hs Negative 4.1 pKd 74
pKd 4.1 [74]
thiochrome