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M1

Previous and Unofficial Names
m1
Structural Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Name Reference
Human 7 460 11q13 CHRM1 6-7
Rat 7 460 1q43-q51 Chrm1 2-5
Mouse 7 460 19 A Chrm1 8-9
Contents:
Previous and Unofficial Names
Structural Information
Database Links
Agonists
Antagonists
Allosteric Regulators
Transduction Mechanisms
Tissue Distribution
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Biologically Significant Variants
Receptor Comments
Database Links
ChEMBL Target 61 (Hs), 11780 (Mm), 10647 (Rn)
Ensembl ENSG00000168539 (Hs), ENSMUSG00000032773 (Mm), ENSRNOG00000018385 (Rn)
Entrez Gene 1128 (Hs), 12669 (Mm), 25229 (Rn)
GeneCards CHRM1 (Hs)
HomoloGene 20189 (Hs)
OMIM 118510 (Hs)
PharmGKB Gene PA26484 (Hs)
Protein Ontology (PRO) PRO:000001613 (Hs)
RefSeq Nucleotide NM_000738 (Hs), NM_007698 (Mm), NM_080773 (Rn)
RefSeq Protein NP_000729 (Hs), NP_031724 (Mm), NP_542951 (Rn)
UniGene Hs. 632119 (Hs)
UniProt P11229 (Hs), P12657 (Mm), P08482 (Rn)
Wikipedia M1
Search for 3D structures on the PDB
Search using keywords: Acetylcholine receptors (muscarinic) M1 Search using accession numbers: P08482 || P11229 || P12657
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
NNC 11-1585 Hs Full agonist 9.9 pKi 39
NNC 11-1607 Hs Full agonist 8.6 pKi 39
pentylthio-TZTP Hs Full agonist 8.6 pKi 80
NNC 11-1314 Hs Full agonist 7.4 pKi 39
xanomeline Hs Partial agonist 6.7 – 7.9 pKi 1,81-83
sabcomeline Hs Partial agonist 6.7 pKi 82
arecaidine propargyl ester Hs Full agonist 6.4 pKi 80
AC-42 Hs Full agonist 6.2 pKi 77
oxotremorine Rn Partial agonist 6.0 pKi 78
arecoline Hs Full agonist 5.7 pKi 80
oxotremorine-M Rn Full agonist 5.6 pKi 78
oxotremorine Hs Partial agonist 5.5 pKi 80
arecoline Rn Partial agonist 5.3 pKi 78
McN-A-343 Rn Partial agonist 5.1 pKi 78
oxotremorine-M Hs Full agonist 5.1 pKi 80
pilocarpine Hs Partial agonist 5.1 pKi 80
acetylcholine Rn Full agonist 5.0 pKi 79
McN-A-343 Hs Partial agonist 4.8 – 5.2 pKi 11
pilocarpine Rn Partial agonist 4.9 pKi 78
milameline Hs Partial agonist 4.8 pKi 82
acetylcholine Hs Full agonist 4.3 – 4.9 pKi 46,80
methylfurmethide Hs Full agonist 4.6 pKi 80
(-)YM796 Hs Partial agonist 4.3 – 4.8 pKi 75
(±)YM796 Hs Partial agonist 4.1 – 4.7 pKi 75
carbachol Hs Full agonist 3.2 – 5.3 pKi 80-82
furmethide Hs Full agonist 4.1 pKi 80
bethanechol Hs Full agonist 4.0 pKi 80
carbachol Rn Full agonist 3.9 pKi 79
bethanechol Rn Full agonist 3.7 pKi 78
(+)aceclidine Hs Full agonist 5.4 pEC50 76
(-)aceclidine Hs Partial agonist 5.0 pEC50 76
View species-specific agonist tables
Agonist Comments
Please consult references [10-14] for further details of the activity of some of the ligands in this list.
Pilocarpine has been found to be a partial agonist [10-11,14] as well as a full agonist [12] at the M1 receptor.
Oxotremorine has been found to be a partial agonist [10-12] as well as a full agonist [11] at the M1 receptor.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]QNB Hs Antagonist 10.6 – 10.8 pKd 6,95
[3H]NMS Rn Antagonist 9.7 pKd 12,79
[3H]NMS Hs Antagonist 8.8 – 10.3 pKd 46,80-81,83,90,92-95
[3H]darifenacin Hs Antagonist 8.8 pKd 96
MT7 (recombinant) Hs Antagonist 11.1 pKi 91
MT7 (mamba venom) Hs Antagonist 11.0 pKi 91
N-methyl scopolamine Hs Antagonist 9.9 pKi 89
propantheline Hs Antagonist 9.7 pKi 85
atropine Rn Antagonist 9.0 – 9.7 pKi 79,84,87
ipratropium Hs Antagonist 9.3 pKi 92
atropine Hs Antagonist 8.5 – 9.6 pKi 6,81,85,89,92,96
scopolamine Hs Antagonist 9.0 pKi 85
4-DAMP Rn Antagonist 8.9 pKi 84
silahexocyclium Rn Antagonist 8.7 pKi 87
hexocyclium Rn Antagonist 8.6 pKi 87
darifenacin Hs Antagonist 8.3 pKi 92
hexahydrodifenidol Rn Antagonist 8.0 pKi 87
pirenzepine Rn Antagonist 7.8 – 7.9 pKi 84,87
methoctramine Rn Antagonist 7.8 pKi 87
HHSiD Hs Antagonist 7.7 pKi 86
HHSiD Rn Antagonist 7.4 – 7.9 pKi 84,87
p-F-HHSiD Hs Antagonist 7.1 – 7.8 pKi 85-86
MT1 Hs Antagonist 7.3 – 7.6 pKi 88-89
pirenzepine Hs Antagonist 6.3 – 8.3 pKi 6,85-86,90
methoctramine Hs Antagonist 7.0 – 7.3 pKi 86,96
MT3 Hs Antagonist 7.1 pKi 90
himbacine Hs Antagonist 6.7 – 7.1 pKi 90,97
MT2 Hs Antagonist 6.4 pKi 88
AF-DX 116 Hs Antagonist 6.2 pKi 86
AF-DX 116 Rn Antagonist 5.9 – 6.3 pKi 84,87
lithocholylcholine Rn Antagonist 5.6 pKi 79
View species-specific antagonist tables
Allosteric Regulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
KT 5720 Hs Positive 6.4 pKd 48
staurosporine Hs Positive 5.9 pKd 48
Gö 7874 Hs Negative 5.8 pKd 48
WIN 51,708 Hs Negative 5.8 pKd 49
KT 5823 Hs Positive 5.7 pKd 48
WIN 62,577 Hs Negative 5.5 pKd 49
brucine Hs Positive 4.5 – 5.7 pKd 80,98
eburnamonine Hs Neutral 5.1 pKd 80
K-252a Hs Positive 5.1 pKd 48
alcuronium Hs Negative 5.0 pKd 80
strychnine Hs Neutral 4.9 – 5.0 pKd 46,80
strychnine Hs Negative 4.9 pKd 46
vincamine Hs Neutral 4.8 pKd 80
brucine Hs Neutral 4.5 pKd 98
N-benzyl brucine Hs Negative 4.4 pKd 98
N-chloromethyl-brucine Hs Negative 4.1 pKd 98
thiochrome Hs Neutral 4.1 pKd 50
brucine N-oxide Hs Neutral 3.2 pKd 98
brucine N-oxide Hs Positive 3.2 pKd 98
AC-42 Hs Negative 6.2 pKi 77
clozapine Hs Positive 7.9 pIC50 99
clozapine Rn Positive 7.7 pIC50 100
N-desmethylclozapine Hs Positive 7.3 pIC50 99
N-desmethylclozapine Rn Positive 6.8 pIC50 100
AC-260584 Rn Positive 5.9 pIC50 100
View species-specific allosteric regulator tables

Explore drug-target interactions for this set of compounds using iPHACE

Primary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
References:  20-23
Tissue Distribution
CNS: cerbral cortex, corpus striatum, hippocampus, thalamus.
Species:  Mouse
Technique:  Radioligand binding.
References:  61
CNS: caudate putamen, nucleus accumbens, olfactory tubercle.
Species:  Rat
Technique:  in situ hybridisation.
References:  51
CNS: pons.
Species:  Rat
Technique:  Radioligand binding.
References:  52
CNS: forebrain.
Species:  Mouse
Technique:  immunocytochemistry.
References:  53
Heart: intrinsic neurons.
Species:  Rat
Technique:  in situ hybridisation.
References:  54
Vestibular system.
Species:  Human
Technique:  RT-PCR.
References:  55
Vestibular system.
Species:  Rat
Technique:  RT-PCR.
References:  55
Esophageal smooth muscle.
Species:  Human
Technique:  Radioligand binding.
References:  56
Bladder.
Species:  Human
Technique:  RT-PCR.
References:  57
CNS: cerebral cortex, basal ganglia, limbic areas.
Species:  Human
Technique:  Radioligand binding.
References:  58
CNS: cranial nerve nuclei.
Species:  Rat
Technique:  in situ hybridisation.
References:  59
CNS: cerebral cortex, hippocampus, corpus striatum, olfactory tubercle, midbrain, pons-medulla, cerebellum.
Species:  Rat
Technique:  Immunoprecipitation.
References:  60
CNS: hippocampus.
Species:  Rat
Technique:  immunocytochemistry.
References:  62
Functional Assays
Measurement of PI levels in mouse Y1 adrenal cells transfected with the mouse M1 receptor.
Species:  Mouse
Tissue:  Y1 adrenal cells.
Response measured:  Stimulation of PI hydrolysis.
References:  8
Measurement of PI hydrolysis, Ca2+ mobilisation and [3H]arachidonic acid release in A9 L cells transfected with the human M1 receptor.
Species:  Human
Tissue:  A9 L cells.
Response measured:  Stimulation of PI hydrolysis, Ca2+ mobilisation and [3H]arachidonic acid release.
References:  38
Measurement of PI hydrolysis in CHO cells transfected with the human M1 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Stimulation of PI hydrolysis.
References:  39
Measurement of ERK1/2 activity in hippocampal cells endogenously expressing the M1 receptor.
Species:  Rat
Tissue:  Post-ischemic hippocampus.
Response measured:  Increase in ERK1/2 activity.
References:  40
Measurement of activation of ERK1/2 in PC12D cells endogeneously expressing the M1 receptor.
Species:  Rat
Tissue:  Neuronal PC12D cells.
Response measured:  Activation of ERK1/2.
References:  41
Measurement of activation of neuronal nitric oxide synthetase in chinese hamster overy cells transfected with the M1 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Activation of nitric oxide synthetase.
References:  42
Measurement of ERK1/2 activity in COS-7 cells transfected with the human M2 receptor.
Species:  Human
Tissue:  COS-7 cells.
Response measured:  Increase in ERK1/2 activity.
References:  43
Measurement of GIRK channel activity in Xenopus oocytes transfected with the human M1 receptor.
Species:  Human
Tissue:  Xenopus oocytes.
Response measured:  Inhibition of GIRK channels.
References:  44
Measurement of the effects of a ligand on the level, or rate, of binding of GTPγ35S to membranes.
Species:  Human
Tissue:  CHO cell membranes.
Response measured:  The binding of GTPγ35S to G proteins coupled to the receptor.
References:  10,45-50
Measurement of the effects of a ligand on the rate of hydrolysis of GTP by G proteins in membranes.
Species:  Human
Tissue:  CHO cells.
Response measured:  Generation of 32Pi from [γ-32P]GTP.
References:  10
Physiological Functions
Bronchoconstriction.
Species:  Human
Tissue:  In vivo.
References:  63
Vasodilation.
Species:  Rat
Tissue:  Lung.
References:  64
Modulation of NMDA receptor-meditated excitatory synaptic transmission.
Species:  Rat
Tissue:  Hippocampal CA1 pyramidal cells.
References:  65
Regulation of circadian rhythms.
Species:  Rat
Tissue:  Hypothalamic suprachiasmatic nucleus.
References:  66
Automaticity of the heart.
Species:  Mouse
Tissue:  Heart.
References:  67
Autoreceptor: modulation of ACh release.
Species:  Rat
Tissue:  Basal forebrain slices.
References:  68
Autoreceptor: modulation of ACh release.
Species:  Human
Tissue:  Neocortex slices.
References:  69
Stimulation of water consumption.
Species:  Rat
Tissue:  In vivo.
References:  70
Hypothermia.
Species:  Rat
Tissue:  In vivo.
References:  71
Spinal analgesia.
Species:  Rat
Tissue:  In vivo.
References:  72
Memory function.
Species:  Rat
Tissue:  In vivo.
References:  73
Stimulation of urination.
Species:  Rat
Tissue:  In vivo.
References:  74
Physiological Consequences of Altering Gene Expression
M1 receptor knockout mice exhibit reduced carbachol-stimulated ion secretion in the colon compared to wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  34
M1 receptor knockout mice exhibit reduced salivary flow.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  29
M1 receptor knockout mice exhibit reduced seizure activity in the pilocarpine model of epilepsy.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  24
M1 receptor knockout mice exhibit loss of regulation of M-current potassium channel activity.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  24
M1 receptor knockout mice exhibit a loss of the positive chronotropic and inotropic responses.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  25
M1 receptor knockout mice exhibit increased locomotor activity and hyperactivity under stress.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  26
M1 receptor knockout mice exhibit increased dopamine levels in the striatum and increased locomotor activity.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  27
M1 receptor knockout mice showed normal or even enhanced memory for tasks that involve matching-to-sample problems but significant impairments in non-matching-to-sample working memory and consolidation.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  28
M1 receptor knockout mice exhibit disrupted tonotopic organisation and frequency tuning in the auditory cortex.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  30-31
M1 receptor knockout mice exhibit reduced gastric pepsinogen secretion.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  32
Hippocampal slices from M1 receptor knockout mice do not exhibit carbachol-induced enhancement of LTP of excitatory synaptic transmission as seen in wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  33
Lung slices from M1 receptor knockout mice exhibit increased agonist-induced bronchoconstriction compared to wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  35
M1 receptor knockout mice exhibit an increased tidal volume of the lung at rest.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  36
Biologically Significant Variants
Cys417 is a highly conserved residue in TM7 and is essential to receptor function. A rare Cys417 -> Arg mutation has been found in the human genome with possible physiological consequences.
Type:  Single nucleotide polymorphism.
Species:  Human
References:  37
Receptor Comments
For reviews on muscarinic receptor knockout mice see [15-19].

To cite this receptor data page, please use the following:

Nigel J. M. Birdsall, David A. Brown, Noel J. Buckley, Arthur Christopoulos, Richard M. Eglen, Frederick Ehlert, Rudolf Hammer, Heinz J. Kilbinger, Günter Lambrecht, Fred Mitchelson, Ernst Mutschler, Neil M. Nathanson, Roy D. Schwarz, Andrew B. Tobin, Jurgen Wess.
Acetylcholine receptors (muscarinic): M1. Last modified on 2010-06-28. Accessed on 2010-09-03. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=13.


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