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 11,99
Mouse 7 460 19 A Chrm1 cholinergic receptor, muscarinic 1, CNS 85,109
Rat 7 460 1q43-q51 Chrm1 cholinergic receptor, muscarinic 1 66,97,117,125
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)
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:  124
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 24
⤷ pKi 9.9 [24]
NNC 11-1607 Hs Full agonist 8.6 pKi 24
⤷ pKi 8.6 [24]
pentylthio-TZTP Hs Full agonist 8.6 pKi 60
⤷ pKi 8.6 [60]
NNC 11-1314 Hs Full agonist 7.4 pKi 24
⤷ pKi 7.4 [24]
xanomeline Hs Partial agonist 6.7 – 7.9 pKi 25,61,132,144
⤷ pKi 6.7 – 7.9 [25,61,132,144]
sabcomeline Hs Partial agonist 6.7 pKi 144
⤷ pKi 6.7 [144]
arecaidine propargyl ester Hs Full agonist 6.4 pKi 60
⤷ pKi 6.4 [60]
LY593093 Hs Partial agonist 6.2 pKi 134
⤷ pKi 6.2 [134]
AC-42 Hs Full agonist 6.2 pKi 70
⤷ pKi 6.2 [70]
oxotremorine Rn Partial agonist 6.0 pKi 87
⤷ pKi 6.0 [87]
arecoline Hs Full agonist 5.7 pKi 60
⤷ pKi 5.7 [60]
oxotremorine-M Rn Full agonist 5.6 pKi 87
⤷ pKi 5.6 [87]
oxotremorine Hs Partial agonist 5.5 pKi 60
⤷ pKi 5.5 [60]
cevimeline Hs Agonist 5.3 pKi 79
⤷ pKi 5.3 (Ki 4.85x10-6 M) [79]
Description: Displacement of [3H]QNB from cloned receptor.
arecoline Rn Partial agonist 5.3 pKi 87
⤷ pKi 5.3 [87]
McN-A-343 Rn Partial agonist 5.1 pKi 87
⤷ pKi 5.1 [87]
oxotremorine-M Hs Full agonist 5.1 pKi 60
⤷ pKi 5.1 [60]
pilocarpine Hs Partial agonist 5.1 pKi 60
⤷ pKi 5.1 [60]
McN-A-343 Hs Partial agonist 4.8 – 5.2 pKi 104
⤷ pKi 4.8 – 5.2 [104]
acetylcholine Rn Full agonist 5.0 pKi 23
⤷ pKi 5.0 [23]
pilocarpine Rn Partial agonist 4.9 pKi 87
⤷ pKi 4.9 [87]
milameline Hs Partial agonist 4.8 pKi 144
⤷ pKi 4.8 [144]
acetylcholine Hs Full agonist 4.3 – 4.9 pKi 60,72
⤷ pKi 4.3 – 4.9 [60,72]
methylfurmethide Hs Full agonist 4.6 pKi 60
⤷ pKi 4.6 [60]
(-)-YM796 Hs Partial agonist 4.3 – 4.8 pKi 135
⤷ pKi 4.3 – 4.8 [135]
(±)YM796 Hs Partial agonist 4.1 – 4.7 pKi 135
⤷ pKi 4.1 – 4.7 [135]
carbachol Hs Full agonist 3.2 – 5.3 pKi 25,60,144
⤷ pKi 3.2 – 5.3 [25,60,144]
furtrethonium Hs Full agonist 4.1 pKi 60
⤷ pKi 4.1 [60]
bethanechol Hs Full agonist 4.0 pKi 60
⤷ pKi 4.0 [60]
carbachol Rn Full agonist 3.9 pKi 23
⤷ pKi 3.9 [23]
bethanechol Rn Full agonist 3.7 pKi 87
⤷ pKi 3.7 [87]
AZD6088 Hs Partial agonist 8.3 pEC50 91
⤷ pEC50 8.3 (EC50 5x10-9 M) [91]
methacholine Rn Agonist 6.4 pEC50 96
⤷ pEC50 6.4 (EC50 4x10-7 M) [96]
(+)-aceclidine Hs Full agonist 5.4 pEC50 32
⤷ pEC50 5.4 [32]
(-)-aceclidine Hs Partial agonist 5.0 pEC50 32
⤷ pEC50 5.0 [32]
[11C]butylthio-TZTP Hs Full agonist - - 35
⤷ [35]
[11C]xanomeline Hs Full agonist - - 35
⤷ [35]
SPP1 N/A Agonist - - 14
⤷ [14]
View species-specific agonist tables
Agonist Comments
Please consult references [16,74,104,130,141] for further details of the activity of some of the ligands in this list.

Pilocarpine has been found to be a partial agonist [74,104,141] as well as a full agonist [130] at the M1 receptor; oxotremorine has also been found to be a partial agonist [74,104,130] as well as a full agonist [104] 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 26,99
⤷ pKd 10.6 – 10.8 (Kd 2.51x10-11 – 1.58x10-11 M) [26,99]
Cy3B-telenzepine Hs Antagonist 10.5 pKd 53
⤷ pKd 10.5 [53]
[3H]N-methyl scopolamine Hs Antagonist 9.4 – 10.3 pKd 22,25-26,55,60-62,64,72
⤷ pKd 9.4 – 10.3 (Kd 4.2x10-10 – 5x10-11 M) [22,25-26,55,60-62,64,72]
[3H]N-methyl scopolamine Rn Antagonist 9.7 pKd 23,130
⤷ pKd 9.7 [23,130]
biperiden Hs Antagonist 9.3 pKd 10
⤷ pKd 9.3 (Kd 4.8x10-10 M) [10]
Alexa-488-telenzepine Hs Antagonist 9.3 pKd 53
⤷ pKd 9.3 [53]
[3H]darifenacin Hs Antagonist 8.8 pKd 113
⤷ pKd 8.8 [113]
[3H]pirenzepine Hs Antagonist 7.9 pKd 133
⤷ pKd 7.9 (Kd 1.4x10-8 M) [133]
[3H]pirenzepine Rn Antagonist 7.7 – 7.9 pKd 34,48
⤷ pKd 7.7 – 7.9 [34,48]
otenzepad Hs Antagonist 6.2 pKd 33
⤷ pKd 6.2 [33]
N-methyl scopolamine Hs Antagonist 9.9 pKi 37
⤷ pKi 9.9 [37]
umeclidinium Hs Antagonist 9.8 pKi 68,107
⤷ pKi 9.8 (Ki 1.6x10-10 M) [68,107]
propantheline Hs Antagonist 9.7 pKi 57
⤷ pKi 9.7 [57]
AE9C90CB Hs Antagonist 9.7 pKi 112
⤷ pKi 9.7 [112]
tiotropium Hs Antagonist 9.6 pKi 30
⤷ pKi 9.6 [30]
[3H](+)telenzepine Rn Antagonist 9.4 pKi 34
⤷ pKi 9.4 [34]
revefenacin Hs Antagonist 9.4 pKi 52
⤷ pKi 9.4 (Ki 4.17x10-10 M) [52]
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 17,23,63
⤷ pKi 9.0 – 9.7 [17,23,63]
ipratropium Hs Antagonist 9.3 pKi 55
⤷ pKi 9.3 [55]
4-DAMP Hs Antagonist 9.2 pKi 31
⤷ pKi 9.2 [31]
dicyclomine Hs Antagonist 9.1 pKi 5
⤷ pKi 9.1 (Ki 8.3x10-10 M) [5]
atropine Hs Antagonist 8.5 – 9.6 pKi 25,37,55,57,99,113
⤷ pKi 8.5 – 9.6 [25,37,55,57,99,113]
benzatropine Rn Antagonist 9.0 pKi 93
⤷ pKi 9.0 (Ki 9.5x10-10 M) [93]
Description: Displacement binding experiment using homogenised rat caudate putamen.
scopolamine Hs Antagonist 9.0 pKi 57
⤷ pKi 9.0 [57]
4-DAMP Rn Antagonist 8.9 pKi 63
⤷ pKi 8.9 [63]
trihexyphenidyl Hs Antagonist 8.9 pKi 5
⤷ pKi 8.9 (Ki 1.35x10-9 M) [5]
tripitramine Hs Antagonist 8.8 pKi 82
⤷ pKi 8.8 [82]
silahexocyclium Rn Antagonist 8.7 pKi 17
⤷ pKi 8.7 [17]
UH-AH 37 Hs Antagonist 8.6 – 8.7 pKi 42,140
⤷ pKi 8.6 – 8.7 [42,140]
hexocyclium Rn Antagonist 8.6 pKi 17
⤷ pKi 8.6 [17]
oxybutynin Hs Antagonist 8.6 pKi 29,58,112
⤷ pKi 8.6 (Ki 2.4x10-9 M) [29,58,112]
tolterodine Hs Antagonist 8.5 – 8.7 pKi 42,112
⤷ pKi 8.5 – 8.7 [42,112]
ethopropazine Rn Antagonist 8.5 pKi 18
⤷ pKi 8.5 (Ki 3.1x10-9 M) [18]
Description: Displacement of [H]QNB binding in rat forebrain brain homogenate.
oxybutynin Rn Antagonist 8.2 pKi 92
⤷ pKi 8.2 [92]
pirenzepine Hs Antagonist 7.8 – 8.3 pKi 17,31,51,57,62,140
⤷ pKi 7.8 – 8.3 [17,31,51,57,62,140]
hexahydrodifenidol Rn Antagonist 8.0 pKi 17
⤷ pKi 8.0 [17]
solifenacin Rn Antagonist 8.0 pKi 92
⤷ pKi 8.0 [92]
darifenacin Hs Antagonist 7.5 – 8.3 pKi 42,51,55,58,112
⤷ pKi 7.5 – 8.3 [42,51,55,58,112]
pirenzepine Rn Antagonist 7.8 – 7.9 pKi 17,63
⤷ pKi 7.8 – 7.9 [17,63]
amitriptyline Hs Antagonist 7.8 pKi 116
⤷ pKi 7.8 (Ki 1.47x10-8 M) [116]
methoctramine Rn Antagonist 7.8 pKi 17
⤷ pKi 7.8 [17]
VU0255035 Hs Antagonist 7.8 pKi 110
⤷ pKi 7.8 (Ki 1.487x10-8 M) [110]
dosulepin Hs Antagonist 7.7 pKi 116
⤷ pKi 7.7 (Ki 1.8x10-8 M) [116]
hexahydrosiladifenidol Hs Antagonist 7.7 pKi 33
⤷ pKi 7.7 [33]
hexahydrosiladifenidol Rn Antagonist 7.4 – 7.9 pKi 17,63
⤷ pKi 7.4 – 7.9 [17,63]
solifenacin Hs Antagonist 7.6 pKi 58,112
⤷ pKi 7.6 [58,112]
AFDX384 Hs Antagonist 7.5 pKi 31
⤷ pKi 7.5 [31]
p-F-HHSiD Hs Antagonist 7.1 – 7.8 pKi 33,57
⤷ pKi 7.1 – 7.8 [33,57]
muscarinic toxin 1 Hs Antagonist 7.3 – 7.6 pKi 37,49
⤷ pKi 7.3 – 7.6 [37,49]
guanylpirenzepine Rn Antagonist 7.3 – 7.6 pKi 3,129
⤷ pKi 7.3 – 7.6 [3,129]
AQ-RA 741 Hs Antagonist 7.2 – 7.5 pKi 31,42
⤷ pKi 7.2 – 7.5 [31,42]
muscarinic toxin 3 Hs Antagonist 7.1 pKi 62
⤷ pKi 7.1 [62]
BODIPY-pirenzepine Hs Antagonist 7.0 pKi 59
⤷ pKi 7.0 [59]
methoctramine Hs Antagonist 6.6 – 7.3 pKi 31,33,51,113
⤷ pKi 6.6 – 7.3 [31,33,51,113]
himbacine Hs Antagonist 6.7 – 7.1 pKi 31,62,89
⤷ pKi 6.7 – 7.1 [31,62,89]
(S)-dimetindene Hs Antagonist 6.7 pKi 20
⤷ pKi 6.7 (Ki 1.906x10-7 M) [20]
Description: Binding to hM1 receptors expressed in CHO cells.
muscarinic toxin 2 Hs Antagonist 6.4 pKi 49
⤷ pKi 6.4 [49]
otenzepad Rn Antagonist 5.9 – 6.3 pKi 17,63
⤷ pKi 5.9 – 6.3 [17,63]
lithocholylcholine Rn Antagonist 5.6 pKi 23
⤷ pKi 5.6 [23]
ML381 Hs Antagonist <5.0 pKi 39
⤷ pKi <5.0 (Ki >1x10-5 M) [39]
glycopyrrolate Hs Antagonist 9.9 pIC50 118
⤷ pIC50 9.9 (IC50 1.26x10-10 M) [118]
Description: Assay uses glycopyrronium bromide
aclidinium Hs Antagonist 9.9 pIC50 102
⤷ pIC50 9.9 (IC50 1.4x10-10 M) [102]
Description: Human M1 receptors expressed in CHO-K1 cells
solifenacin Hs Antagonist 7.2 pIC50 101
⤷ pIC50 7.2 (IC50 6.35x10-8 M) [101]
[18F](R,R)-quinuclidinyl-4-fluoromethyl-benzilate Rn Antagonist - - 65
⤷ [65]
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 [94]).

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 [18], 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 1-2,21,81
⤷ pKB 4.0 – 4.8 [1-2,21,81]
KT 5720 Hs Positive 6.4 pKd 76
⤷ pKd 6.4 (Kd 3.98x10-7 M) [76]
staurosporine Hs Positive 5.9 pKd 76
⤷ pKd 5.9 [76]
Gö 7874 Hs Negative 5.8 pKd 76
⤷ pKd 5.8 [76]
WIN 51,708 Hs Negative 5.8 pKd 77
⤷ pKd 5.8 [77]
KT 5823 Hs Positive 5.7 pKd 76
⤷ pKd 5.7 [76]
WIN 62,577 Hs Negative 5.5 pKd 77
⤷ pKd 5.5 [77]
brucine Hs Positive 4.5 – 5.8 pKd 60,75
⤷ pKd 4.5 – 5.8 (Kd 3x10-5 – 1.78x10-6 M) [60,75]
K-252a Hs Positive 5.1 pKd 76
⤷ pKd 5.1 [76]
vinburnine Hs Neutral 5.1 pKd 60
⤷ pKd 5.1 [60]
alcuronium Hs Negative 5.0 pKd 60
⤷ pKd 5.0 [60]
strychnine Hs Neutral 4.9 – 5.0 pKd 60,72
⤷ pKd 4.9 – 5.0 [60,72]
strychnine