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M4 receptor

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Target id: 16

Nomenclature: M4 receptor

Family: Acetylcholine receptors (muscarinic)

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 7 479 11p11.2 CHRM4 cholinergic receptor muscarinic 4 3,34
Mouse 7 479 2 50.63 cM Chrm4 cholinergic receptor, muscarinic 4 58
Rat 7 478 3q24 Chrm4 cholinergic receptor, muscarinic 4 45,91,105
Previous and Unofficial Names Click here for help
HM3 [73-74] | Chrm-4 | cholinergic receptor, muscarinic 4 | cholinergic receptor
Database Links Click here for help
Specialist databases
GPCRDB acm4_human (Hs), acm4_mouse (Mm)
Other databases
Alphafold
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the M4 muscarinic acetylcholine receptor (M4-mT4L) bound to tiotropium.
PDB Id:  5DSG
Ligand:  tiotropium
Resolution:  2.6Å
Species:  Human
References:  89
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]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 8.2 pKd 51
pKd 8.2 [51]
pentylthio-TZTP Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.7 pKi 43
pKi 8.7 [43]
NNC 11-1585 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.6 pKi 16
pKi 8.6 [16]
NNC 11-1607 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.1 pKi 16
pKi 8.1 [16]
xanomeline Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 7.4 – 7.7 pKi 99,106
pKi 7.4 – 7.7 [99,106]
NNC 11-1314 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.3 pKi 16
pKi 7.3 [16]
sabcomeline Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 7.2 pKi 106
pKi 7.2 [106]
McN-A-343 Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 5.6 – 6.7 pKi 48
pKi 5.6 – 6.7 [48]
cevimeline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 6.0 pKi 57
pKi 6.0 (Ki 1.012x10-6 M) [57]
Description: Displacement of [3H]QNB from cloned receptor.
arecaidine propargyl ester Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.9 pKi 43
pKi 5.9 [43]
methacholine Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Rn Agonist 5.8 pKi 72,76
pKi 5.8 (Ki 1.6x10-6 M) [72,76]
arecoline Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.5 pKi 43,71,76
pKi 5.5 [43,71,76]
milameline Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 5.5 pKi 106
pKi 5.5 [106]
oxotremorine Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.2 pKi 43,76
pKi 5.2 [43,76]
oxotremorine-M Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.2 pKi 43
pKi 5.2 [43]
pilocarpine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 5.2 pKi 43,76
pKi 5.2 [43,76]
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 4.5 – 5.6 pKi 43,46
pKi 4.5 – 5.6 [43,46]
methylfurmethide Small molecule or natural product Click here for species-specific activity table Hs Full agonist 4.7 pKi 43
pKi 4.7 [43]
carbachol Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 4.3 – 4.9 pKi 43,106
pKi 4.3 – 4.9 [43,106]
furtrethonium Small molecule or natural product Click here for species-specific activity table Hs Full agonist 4.3 pKi 43
pKi 4.3 [43]
bethanechol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 4.0 pKi 43,76
pKi 4.0 [43,76]
(+)-aceclidine Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.4 pEC50 26
pEC50 5.4 [26]
(-)-aceclidine Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 4.8 pEC50 26
pEC50 4.8 [26]
iperoxo Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Agonist - - 79
[79]
View species-specific agonist tables
Agonist Comments
The binding data for McN-A-343 [48] is found on rat striatum.
Please consult references [5,52,76,98] for further details of the activity of some of the ligands in this list.
McN-A-343 and pilocarpine have been found to be partial agonists [52] and full agonists [76,98] at the M4 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 9.7 – 10.5 pKd 42,73
pKd 9.7 – 10.5 (Kd 2x10-10 – 3.16x10-11 M) [42,73]
[3H]N-methyl scopolamine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 9.9 – 10.2 pKd 10,42-43,47,50,98
pKd 9.9 – 10.2 (Kd 1.4x10-10 – 6x10-11 M) [10,42-43,47,50,98]
[3H]AF DX-384 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 8.7 pKd 11,62,94
pKd 8.7 [11,62,94]
biperiden Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.6 pKd 2
pKd 8.6 (Kd 2.4x10-9 M) [2]
otenzepad Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.0 pKd 27
pKd 7.0 [27]
tiotropium Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 10.2 – 10.6 pKi 86,88
pKi 10.2 – 10.6 [86,88]
3-quinuclidinyl-benzilate Small molecule or natural product Hs Antagonist 10.4 pKi 9
pKi 10.4 (Ki 4x10-11 M) [9]
umeclidinium Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 10.3 pKi 78
pKi 10.3 [78]
propantheline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 10.2 pKi 41
pKi 10.2 [41]
aclidinium Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 10.0 pKi 88
pKi 10.0 [88]
oxyphenonium Small molecule or natural product Approved drug Hs Antagonist 9.8 pKi 9
pKi 9.8 (Ki 1.45x10-10 M) [9]
atropine Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 9.7 pKi 45
pKi 9.7 [45]
glycopyrrolate Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 9.1 – 10.0 pKi 84,86
pKi 9.1 – 10.0 [84,86]
AE9C90CB Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.5 pKi 81
pKi 9.5 [81]
mepenzolic acid Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 9.4 pKi 9
pKi 9.4 (Ki 3.6x10-10 M) [9]
scopolamine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 9.1 – 9.5 pKi 2,41
pKi 9.1 – 9.5 [2,41]
revefenacin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 9.3 pKi 38
pKi 9.3 (Ki 5.5x10-10 M) [38]
Description: Determined from a radioligand binding assay using membranes from CHO‐K1 cells expressing the hM4 receptor, and displacement of [3H]NMS tracer.
ipratropium Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 9.2 pKi 39
pKi 9.2 [39]
4-DAMP Small molecule or natural product Click here for species-specific activity table Rn Antagonist 9.1 pKi 45
pKi 9.1 [45]
atropine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.7 – 9.5 pKi 18,39,41,74
pKi 8.7 – 9.5 [18,39,41,74]
4-DAMP Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.9 pKi 24
pKi 8.9 [24]
oxybutynin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.4 – 8.7 pKi 23,81
pKi 8.4 – 8.7 [23,81]
muscarinic toxin 3 Peptide Click here for species-specific activity table Hs Antagonist 8.5 pKi 9
pKi 8.5 (Ki 3x10-9 M) [9]
silahexocyclium Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.5 pKi 6
pKi 8.5 [6]
tolterodine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.3 – 8.4 pKi 31,81
pKi 8.3 – 8.4 [31,81]
UH-AH 37 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.3 – 8.4 pKi 31,104
pKi 8.3 – 8.4 [31,104]
hexocyclium Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.3 pKi 6
pKi 8.3 [6]
dicyclomine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.3 pKi 9
pKi 8.3 (Ki 5x10-9 M) [9]
PCS1055 Small molecule or natural product Hs Antagonist 8.2 pKi 18
pKi 8.2 [18]
himbacine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.9 – 8.4 pKi 9,24,44,61
pKi 8.4 (Ki 4x10-9 M) [9]
pKi 7.9 – 8.2 [24,44,61]
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 8.1 pKi 82
pKi 8.1 (Ki 7.2x10-9 M) [82]
AQ-RA 741 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.8 – 8.2 pKi 24,31
pKi 7.8 – 8.2 [24,31]
tripitramine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.9 pKi 63
pKi 7.9 [63]
darifenacin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.3 – 8.1 pKi 31,39,81
pKi 7.3 – 8.1 [31,39,81]
hexahydrosiladifenidol Small molecule or natural product Click here for species-specific activity table Rn Antagonist 7.7 pKi 45
pKi 7.7 [45]
AFDX384 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.3 – 8.0 pKi 18,24
pKi 7.3 – 8.0 [18,24]
pirenzepine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.0 – 8.1 pKi 9,24,37,41,44,104
pKi 8.1 (Ki 8x10-9 M) [9]
pKi 7.0 – 7.6 [24,37,41,44,104]
PD 102807 Small molecule or natural product Hs Antagonist 7.4 – 7.6 pKi 18,68
pKi 7.4 – 7.6 [18,68]
p-F-HHSiD Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.1 – 7.5 pKi 27,41
pKi 7.1 – 7.5 [27,41]
dosulepin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.2 pKi 82
pKi 7.2 (Ki 6.1x10-8 M) [82]
hexahydrosiladifenidol Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.5 – 7.7 pKi 6,27
pKi 6.5 – 7.7 [6,27]
muscarinic toxin 1 Peptide Click here for species-specific activity table Hs Antagonist 7.1 pKi 35
pKi 7.1 [35]
hexahydrodifenidol Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.1 pKi 6
pKi 7.1 [6]
pirenzepine Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 7.1 pKi 45
pKi 7.1 [45]
methoctramine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.6 – 7.5 pKi 6,24,27,37
pKi 6.6 – 7.5 [6,24,27,37]
tropicamide Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 6.9 pKi 9
pKi 6.9 [9]
solifenacin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 6.8 pKi 81
pKi 6.8 [81]
(S)-dimetindene Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 6.5 pKi 8
pKi 6.5 (Ki 2.951x10-7 M) [8]
Description: Binding to hM4 receptors expressed in CHO cells.
otenzepad Small molecule or natural product Click here for species-specific activity table Rn Antagonist 6.5 pKi 45
pKi 6.5 [45]
guanylpirenzepine Small molecule or natural product Click here for species-specific activity table Rn Antagonist 6.2 pKi 97
pKi 6.2 [97]
muscarinic toxin 2 Peptide Click here for species-specific activity table Hs Antagonist 5.9 pKi 35
pKi 5.9 [35]
VU0255035 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.9 pKi 80
pKi 5.9 [80]
lithocholylcholine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.3 pKi 13
pKi 5.3 [13]
muscarinic toxin 7 Peptide Click here for species-specific activity table Hs Antagonist <5.0 pKi 64
pKi <5.0 [64]
ML381 Small molecule or natural product Click here for species-specific activity table Hs Antagonist >4.5 pKi 30
pKi >4.5 (Ki <3x10-5 M) [30]
View species-specific antagonist tables
Antagonist Comments
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 [2].
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
LY2033298 Small molecule or natural product Click here for species-specific activity table Hs Positive 4.9 – 5.5 pKB 12,85
pKB 4.9 – 5.5 [12,85]
KT 5720 Small molecule or natural product Click here for species-specific activity table Hs Neutral 6.4 pKd 54
pKd 6.4 [54]
WIN 51,708 Small molecule or natural product Click here for species-specific activity table Hs Negative 6.2 pKd 55
pKd 6.2 [55]
WIN 62,577 Small molecule or natural product Click here for species-specific activity table Hs Negative 5.9 pKd 55
pKd 5.9 [55]
Gö 7874 Small molecule or natural product Click here for species-specific activity table Hs Neutral 5.7 pKd 54
pKd 5.7 [54]
alcuronium Small molecule or natural product Click here for species-specific activity table Hs Negative 5.6 pKd 43
pKd 5.6 [43]
LY2119620 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Positive 5.5 pKd 19
pKd 5.5 [19]
brucine Small molecule or natural product Click here for species-specific activity table Hs Negative 4.7 – 6.0 pKd 43,53
pKd 4.7 – 6.0 [43,53]
staurosporine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Neutral 5.3 pKd 54
pKd 5.3 [54]
strychnine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Positive 4.8 – 5.0 pKd 43,50
pKd 4.8 – 5.0 [43,50]
vinburnine Small molecule or natural product Click here for species-specific activity table Hs Positive 4.6 pKd 43
pKd 4.6 [43]
N-benzyl brucine Small molecule or natural product Click here for species-specific activity table Hs Negative 4.5 pKd 53
pKd 4.5 [53]
N-benzyl brucine Small molecule or natural product Click here for species-specific activity table Hs Neutral 4.5 pKd 53
pKd 4.5 [53]
N-chloromethyl-brucine Small molecule or natural product Click here for species-specific activity table Hs Neutral 4.4 pKd 53
pKd 4.4 [53]
vincamine Small molecule or natural product Click here for species-specific activity table Hs Positive 4.2 pKd 43
pKd 4.2 [43]
thiochrome Small molecule or natural product Click here for species-specific activity table Hs Positive 4.0 pKd 51
pKd 4.0 [51]
brucine N-oxide Small molecule or natural product Click here for species-specific activity table Hs Neutral 3.6 pKd 53
pKd 3.6 [53]
brucine N-oxide Small molecule or natural product Click here for species-specific activity table Hs Positive 3.6 pKd 53
pKd 3.6 [53]
muscarinic toxin 3 Peptide Click here for species-specific activity table Hs Negative 8.7 pKi 44,67
pKi 8.7 [44,67]
VU0152100 Small molecule or natural product Rn Positive 6.4 pEC50 4
pEC50 6.4 (EC50 3.8x10-7 M) [4]
VU0152099 Small molecule or natural product Rn Positive 6.4 pEC50 4
pEC50 6.4 (EC50 4.03x10-7 M) [4]
VU0010010 Small molecule or natural product Hs Positive - - 17
[17]
View species-specific allosteric modulator tables
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Adenylyl cyclase inhibition
References:  60,73
Tissue Distribution Click here for help
Esophageal smooth muscle.
Species:  Human
Technique:  Radioligand binding.
References:  75
Bladder.
Species:  Human
Technique:  RT-PCR.
References:  92
CNS: forebrain.
Species:  Mouse
Technique:  immunocytochemistry.
References:  40
CNS: cerebral cortex, corpus striatum, thalamus, hypothalamus, pons-medulla.
Species:  Mouse
Technique:  Radioligand binding.
References:  65
Heart: intrinsic neurons.
Species:  Rat
Technique:  in situ hybridisation.
References:  36
CNS: basal forebrain, pedunculopontine and laterodorsal tegmental nuclei.
Species:  Rat
Technique:  in situ hybridisation.
References:  95
CNS: cerebral cortex, hippocampus, corpus striatum, olfactory tubercle, midbrain, pons-medulla, cerebellum.
Species:  Rat
Technique:  Immunoprecipitation.
References:  107
CNS: caudate putamen, nucleus accumbens, olfactory tubercle.
Species:  Rat
Technique:  in situ hybridisation.
References:  100
CNS: hippocampus.
Species:  Rat
Technique:  immunocytochemistry.
References:  56
Vestibular system.
Species:  Rat
Technique:  RT-PCR.
References:  96
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Measurement of IP1 levels in murine fibroblast cells (B82) transfected with the rat M4 receptor.
Species:  Rat
Tissue:  B82 cells.
Response measured:  Stimulation of IP1 accumulation.
References:  45
Measurement of cAMP levels in murine fibroblast cells (B82) transfected with the rat M4 receptor.
Species:  Rat
Tissue:  B82 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  45
Measurement of cAMP levels in JEG-3 cells transfected with the human M2 receptor, using a cAMP response element (CRE)-coupled luciferase construct as the reporter.
Species:  Human
Tissue:  JEG-3 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  60
Measurement of cAMP levels in CHO cells transfected with the human M4 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Inhibition of cAMP accumulation.
References:  16
Measurement of ERK1/2 activity in COS-7 cells transfected with the human M4 receptor.
Species:  Human
Tissue:  COS-7 cells.
Response measured:  Increase in ERK1/2 activity.
References:  77
Measurement of Ca2+ channel activity in rat superior cervical ganglion neurons endogenously expressing the M4 receptor.
Species:  Rat
Tissue:  Superior cervical ganglion neurons.
Response measured:  Inhibition of Ca2+ channels.
References:  28-29
Measurement of AC activity in rat striatal homogenates endogenously expressing the M4 receptor.
Species:  Rat
Tissue:  Corpus striatum.
Response measured:  Inhibition of AC activity.
References:  25,66
Measurement of the effects of a ligand on the level, or rate, of binding of GTPγ35S to membranes.
Species:  Human
Tissue:  CHO cells.
Response measured:  The binding of GTPγ35S to G proteins coupled to the receptor.
References:  1,49-52,54-55
Measurement of the effects of a ligand on the rate of hydrolysis of GTP by G proteins in membranes.
Species:  Human
Tissue:  CHO cell membranes.
Response measured:  Generation of 32Pi from [γ-32P]GTP.
References:  1,52
Physiological Functions Click here for help
Autoreceptor: modulation of acetylcholine release.
Species:  Rat
Tissue:  Urinary bladder.
References:  20
Autoreceptor: modulation of acetylcholine release.
Species:  Human
Tissue:  Urinary bladder detrusor muscle.
References:  21
Contraction.
Species:  Rat
Tissue:  Urinary bladder detrusor muscle.
References:  70
Inhibition of dopaminergic (D1 receptor) signalling.
Species:  Rat
Tissue:  Nucleus accumbens.
References:  69
Cell migration.
Species:  Human
Tissue:  Keratinocytes.
References:  15
Physiological Consequences of Altering Gene Expression Click here for help
M4 receptor knockout mice exhibit an increase in anxiolysis compared to wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  22
Hippocampal, cortical and striatal brain slices from M2/M4 double knockout mice lack muscarinic agonist-induced inhibition of acetylcholine release that is seen with wild-type brain slices.
Striatal slices from M4 receptor single knockout mice exhibit the same loss of inhibition of acetylcholine release, but the inhibition remains intact in the hippocampal and cortical slices.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  108
Smooth muscle preparations (gallbladder) from M4 receptor knockout mice exhibit reduced agonist-induced contractions compared to wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  83
Vas deferens tissue from M4 receptor knockout mice exhibits reduced agonist-induced inhibition of noradrenaline release compared to wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  90
Striatal slices from M4 receptor knockout mice exhibit abolished agonist-induced potentiation of dopamine release.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  109
M4 receptor knockout mice exhibit enhanced dopaminergic locomotor activity.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  32-33
Epidermal keratinocytes from M4 receptor knockout mice exhibit reduced agonist-induced migration compared to keratinocytes from wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  15
M4 receptor knockout mice exhibit increased basal hippocampal acetylcholine levels compared to wild-type mice.
M2/M4 double knockout mice exhibit a further increase in basal acetylcholine levels.
In addition, M4 and M2/M4 knockout mice exhibit an increase in hippocampal acetylcholine release in response to a novel environment.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  93
M4 receptor knockout mice exhibit a significantly reduced wound epithelialisation rate compared to wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  14
Smooth muscle from the small intestine of M4 receptor knockout mice do not exhibit any alteration in EFS-induced acetylcholine release.
However, M2/M4 double knockout mice exhibit an increase in acetylcholine release.
Overall, it is thought that both M2 and M4 receptors mediate the autoinhibitory control of acetylcholine release in the mouse ileum, and that each can compensate for loss of the other.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  87
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Chrm4tm1Minm Chrm4tm1Minm/Chrm4tm1Minm
involves: 129X1/SvJ * DBA/2J
MGI:88399  MP:0009745 abnormal behavioral response to xenobiotic PMID: 12729838 
Chrm2tm1Jwe|Chrm4tm1Jwe Chrm2tm1Jwe/Chrm2tm1Jwe,Chrm4tm1Jwe/Chrm4tm1Jwe
involves: 129S4/SvJae * 129S6/SvEvTac * CF-1
MGI:88397  MGI:88399  MP:0004994 abnormal brain wave pattern PMID: 16110248 
Chrm4tm1Jwe Chrm4tm1Jwe/Chrm4tm1Jwe
involves: 129S6/SvEvTac * CF-1
MGI:88399  MP:0002206 abnormal CNS synaptic transmission PMID: 15919709 
Chrm1tm1Jwe|Chrm4tm1Jwe Chrm1tm1Jwe/Chrm1tm1Jwe,Chrm4tm1Jwe/Chrm4tm1Jwe
involves: 129S6/SvEvTac * CF-1
MGI:88396  MGI:88399  MP:0002206 abnormal CNS synaptic transmission PMID: 15919709 
Chrm2tm1Jwe|Chrm4tm1Jwe Chrm2tm1Jwe/Chrm2tm1Jwe,Chrm4tm1Jwe/Chrm4tm1Jwe
involves: 129S4/SvJae * 129S6/SvEvTac * CF-1
MGI:88397  MGI:88399  MP:0002206 abnormal CNS synaptic transmission PMID: 15919709 
Chrm4tm1Jwe Chrm4tm1Jwe/Chrm4tm1Jwe
involves: 129S6/SvEvTac * CF-1
MGI:88399  MP:0005085 abnormal gallbladder physiology PMID: 11961069 
Chrm4tm1Jwe Chrm4tm1Jwe/Chrm4tm1Jwe
involves: 129S6/SvEvTac * CF-1
MGI:88399  MP:0001629 abnormal heart rate PMID: 10688600 
Chrm4tm1Minm Chrm4tm1Minm/Chrm4tm1Minm
involves: 129X1/SvJ * DBA/2J
MGI:88399  MP:0001392 abnormal locomotor activity PMID: 12729838 
Chrm4tm2.1Jwe|Tg(Drd1a-cre)AGsc Chrm4tm2.1Jwe/Chrm4tm2.1Jwe,Tg(Drd1a-cre)AGsc/0
involves: 129S6/SvEvTac * C57BL/6 * FVB/N
MGI:3761815  MGI:88399  MP:0004811 abnormal neuron physiology PMID: 20147565 
Chrm4tm1Jwe Chrm4tm1Jwe/Chrm4tm1Jwe
B6.129S6-Chrm4
MGI:88399  MP:0001529 abnormal vocalization PMID: 18382674 
Chrm4tm2.1Jwe|Tg(Drd1a-cre)AGsc Chrm4tm2.1Jwe/Chrm4tm2.1Jwe,Tg(Drd1a-cre)AGsc/0
involves: 129S6/SvEvTac * C57BL/6 * FVB/N
MGI:3761815  MGI:88399  MP:0002822 catalepsy