Target Information

Target General Information

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Target ID

T67684 (Former ID: TTDS00004)

Target Name

Muscarinic acetylcholine receptor M3 (CHRM3)

Synonyms

M3 receptor; CHRM3

Gene Name

CHRM3

Target Type

Successful target

[1]

Disease

[+] 10 Target-related Diseases

Asthma [ICD-11: CA23]

Chronic obstructive pulmonary disease [ICD-11: CA22]

Functional bladder disorder [ICD-11: GC50]

Glaucoma [ICD-11: 9C61]

Nausea/vomiting [ICD-11: MD90]

Peptic ulcer [ICD-11: DA61]

Respiratory system disease [ICD-11: CB40-CB7Z]

Sebaceous gland disorder [ICD-11: ED91]

Sjogren syndrome [ICD-11: 4A43]

Tonus and reflex abnormality [ICD-11: MB47]

Function

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.

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BioChemical Class

GPCR rhodopsin

UniProt ID

ACM3_HUMAN

Sequence

MTLHNNSTTSPLFPNISSSWIHSPSDAGLPPGTVTHFGSYNVSRAAGNFSSPDGTTDDPL
GGHTVWQVVFIAFLTGILALVTIIGNILVIVSFKVNKQLKTVNNYFLLSLACADLIIGVI
SMNLFTTYIIMNRWALGNLACDLWLAIDYVASNASVMNLLVISFDRYFSITRPLTYRAKR
TTKRAGVMIGLAWVISFVLWAPAILFWQYFVGKRTVPPGECFIQFLSEPTITFGTAIAAF
YMPVTIMTILYWRIYKETEKRTKELAGLQASGTEAETENFVHPTGSSRSCSSYELQQQSM
KRSNRRKYGRCHFWFTTKSWKPSSEQMDQDHSSSDSWNNNDAAASLENSASSDEEDIGSE
TRAIYSIVLKLPGHSTILNSTKLPSSDNLQVPEEELGMVDLERKADKLQAQKSVDDGGSF
PKSFSKLPIQLESAVDTAKTSDVNSSVGKSTATLPLSFKEATLAKRFALKTRSQITKRKR
MSLVKEKKAAQTLSAILLAFIITWTPYNIMVLVNTFCDSCIPKTFWNLGYWLCYINSTVN
PVCYALCNKTFRTTFKMLLLCQCDKKKRRKQQYQQRQSVIFHKRAPEQAL

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3D Structure

Click to Show 3D Structure of This Target

AlphaFold

ADReCS ID

BADD_A05818

HIT2.0 ID

T93KNA

Drugs and Modes of Action

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Approved Drug(s)

[+] 13 Approved Drugs

ACECLIDINE

Drug Info

Approved

Glaucoma/ocular hypertension

[2], [3]

Cevimeline

Drug Info

Approved

Sjogren syndrome

[4]

Darifenacin

Drug Info

Approved

Overactive bladder

[5], [6], [7]

Ipratropium

Drug Info

Approved

Obstructive lung disease

[8], [9]

LAS-34273

Drug Info

Approved

Chronic obstructive pulmonary disease

[10], [11]

Methacholine Chloride

Drug Info

Approved

bronchial hyperreactivity

[3]

Methscopolamine Bromide

Drug Info

Approved

Nausea and vomiting

[3]

Methylscopolamine

Drug Info

Approved

Peptic ulcer

[3], [12], [13]

SMT-D002

Drug Info

Approved

Seborrhea

[14]

Solifenacin

Drug Info

Approved

Overactive bladder

[15], [16]

Succinylcholine

Drug Info

Approved

Spasm

[3], [17], [18]

Tiotropium

Drug Info

Approved

Chronic obstructive pulmonary disease

[19], [6]

Tolterodine

Drug Info

Approved

Overactive bladder

[3]

Clinical Trial Drug(s)

[+] 3 Clinical Trial Drugs

Tarafenacin

Drug Info

Phase 2

Overactive bladder

[20]

TRN-157

Drug Info

Phase 2

Chronic obstructive pulmonary disease

[21]

CHF 5407

Drug Info

Phase 1

Chronic obstructive pulmonary disease

[22]

Discontinued Drug(s)

[+] 4 Discontinued Drugs

Zamifenacin

Drug Info

Discontinued in Phase 3

Urinary incontinence

[23]

PSD-506

Drug Info

Discontinued in Phase 2

Overactive bladder

[24]

Revatropate

Drug Info

Discontinued in Phase 1

Chronic obstructive pulmonary disease

[25]

Alvameline

Drug Info

Terminated

Alzheimer disease

[26]

Mode of Action

[+] 5 Modes of Action

Inhibitor

[+] 36 Inhibitor drugs

ACECLIDINE

Drug Info

[27]

1'-Benzyl-3-phenyl-[3,4']bipiperidinyl-2,6-dione

Drug Info

[48]

1,1-diphenyl-2-(3-tropanyl)ethanol

Drug Info

[49]

1-Methyl-1-(4-pyrrolidin-1-yl-but-2-ynyl)-urea

Drug Info

[50]

2,8-Dimethyl-1-oxa-8-aza-spiro[4.5]decan-3-one

Drug Info

[51]

2-Methyl-6-pyrrolidin-1-yl-hex-4-ynal oxime

Drug Info

[52]

3-(3-benzylamino)-piperidin-2-one

Drug Info

[53]

3-Methyl-7-pyrrolidin-1-yl-hept-5-yn-2-one

Drug Info

[52]

3-Tetrazol-2-yl-1-aza-bicyclo[2.2.2]octane

Drug Info

[54]

4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one

Drug Info

[55]

6-Dimethylamino-2-methyl-hex-4-ynal oxime

Drug Info

[52]

7-Dimethylamino-3-methyl-hept-5-yn-2-one

Drug Info

[52]

7-Dimethylamino-hept-5-yn-2-one

Drug Info

[52]

7-Pyrrolidin-1-yl-hept-5-yn-2-one

Drug Info

[52]

A-987306

Drug Info

[58]

Acetic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester

Drug Info

[59]

Benzoic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester

Drug Info

[61]

BRL-55473

Drug Info

[62]

Cremastrine

Drug Info

[64]

FLUMEZAPINE

Drug Info

[67]

FM1-10

Drug Info

[68]

FM1-43

Drug Info

[68]

GNF-PF-5618

Drug Info

[69]

ISOCLOZAPINE

Drug Info

[73]

ISOLOXAPINE

Drug Info

[74]

N-(4-Dimethylamino-but-2-ynyl)-N-methyl-acetamide

Drug Info

[52]

N-methoxyquinuclidine-3-carboximidoyl chloride

Drug Info

[62]

N-methoxyquinuclidine-3-carboximidoyl fluoride

Drug Info

[62]

NOCARDIMICIN A

Drug Info

[69]

Nocardimicin C

Drug Info

[69]

Nocardimicin D

Drug Info

[69]

Nocardimicin F

Drug Info

[69]

Noccardimicin E

Drug Info

[69]

Propionic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester

Drug Info

[61]

SULFOARECOLINE

Drug Info

[82]

UCB-101333-3

Drug Info

[85]

Agonist

[+] 12 Agonist drugs

Cevimeline

Drug Info

[28]

SMT-D002

Drug Info

[35]

arecaidine propargyl ester

Drug Info

[60]

furtrethonium

Drug Info

[60]

J-104135

Drug Info

[43]

McN-A-343

Drug Info

[76]

methylfurmethide

Drug Info

[60]

NNC 11-1314

Drug Info

[78]

NNC 11-1585

Drug Info

[78]

NNC 11-1607

Drug Info

[78]

pentylthio-TZTP

Drug Info

[60]

[3H]oxotremorine-M

Drug Info

[60]

Antagonist

[+] 27 Antagonist drugs

Darifenacin

Drug Info

[29], [30]

LAS-34273

Drug Info

[25]

Methylscopolamine

Drug Info

[34]

Solifenacin

Drug Info

[36]

Succinylcholine

Drug Info

[37], [38]

Tiotropium

Drug Info

[1], [39]

Tolterodine

Drug Info

[40], [41]

Tarafenacin

Drug Info

[42]

TRN-157

Drug Info

[43]

Zamifenacin

Drug Info

[45]

3-(1-carbamoyl-1,1-diphenylmethyl)-1-(4-methoxyphenylethyl)pyrrolidine (APP)

Drug Info

[40]

4-DAMP

Drug Info

[56], [57]

AE-9C90CB

Drug Info

[43]

guanylpirenzepine

Drug Info

[71]

hexahydrodifenidol

Drug Info

[72]

hexahydrosiladifenidol

Drug Info

[72]

lithocholylcholine

Drug Info

[75]

ML381

Drug Info

[77]

Olterodine

Drug Info

[79]

Oxybutynine

Drug Info

[80]

p-F-HHSiD

Drug Info

[81]

PTAC

Drug Info

[79]

silahexocyclium

Drug Info

[72]

tripitramine

Drug Info

[84]

UH-AH 37

Drug Info

[86]

VU0255035

Drug Info

[87]

[3H]QNB

Drug Info

[89]

Modulator

[+] 9 Modulator drugs

Ipratropium

Drug Info

[31]

Methacholine Chloride

Drug Info

[32]

Methscopolamine Bromide

Drug Info

[33]

CHF 5407

Drug Info

[44]

PSD-506

Drug Info

[46]

Revatropate

Drug Info

[47]

Alvameline

Drug Info

[26]

DAU-5750

Drug Info

[65]

DAU-5884

Drug Info

[66]

Modulator (allosteric modulator)

[+] 8 Modulator (allosteric modulator) drugs

brucine

Drug Info

[63]

Go7874

Drug Info

[70]

N-benzyl brucine

Drug Info

[63]

N-chloromethyl-brucine

Drug Info

[63]

thiochrome

Drug Info

[83]

vinburnine

Drug Info

[60]

WIN 51,708

Drug Info

[88]

WIN 62,577

Drug Info

[88]

Chemical Structure based Activity Landscape of Target

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Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

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Co-Targets

Co-Targets Info

Target Poor or Non Binders

Top

Target Poor or Non Binders

Target Poor or Non Binders Info

Target Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 8 KEGG Pathways

Calcium signaling pathway

Neuroactive ligand-receptor interaction

Cholinergic synapse

Regulation of actin cytoskeleton

Insulin secretion

Salivary secretion

Gastric acid secretion

Pancreatic secretion

Panther Pathway

[+] 3 Panther Pathways

Alzheimer disease-amyloid secretase pathway

Heterotrimeric G-protein signaling pathway-Gq alpha and Go alpha mediated pathway

Muscarinic acetylcholine receptor 1 and 3 signaling pathway

Pathwhiz Pathway

[+] 1 Pathwhiz Pathways

Gastric Acid Production

Reactome

[+] 3 Reactome Pathways

Muscarinic acetylcholine receptors

Acetylcholine regulates insulin secretion

G alpha (q) signalling events

WikiPathways

[+] 9 WikiPathways

Monoamine GPCRs

Calcium Regulation in the Cardiac Cell

Regulation of Actin Cytoskeleton

GPCRs, Class A Rhodopsin-like

Gastrin-CREB signalling pathway via PKC and MAPK

Integration of energy metabolism

GPCR ligand binding

GPCR downstream signaling

GPCRs, Other

Target-Related Models and Studies

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Target Validation

Target Validation Info

Target QSAR Model

References

Top

REF 1

DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.

REF 2

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 288).

REF 3

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015

REF 4

Therapeutic effect of cevimeline on dry eye in patients with Sj gren's syndrome: a randomized, double-blind clinical study. Am J Ophthalmol. 2004 Jul;138(1):6-17.

REF 5

REF 6

Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.

REF 7

2004 approvals: the demise of the blockbuster. Nat Rev Drug Discov. 2005 Feb;4(2):93-4.

REF 8

REF 9

Emerging drugs for postoperative ileus. Expert Opin Emerg Drugs. 2007 Nov;12(4):619-26.

REF 10

Nat Rev Drug Discov. 2013 Feb;12(2):87-90.

REF 11

Aclidinium bromide, a novel long-acting muscarinic M3 antagonist for the treatment of COPD. Curr Opin Investig Drugs. 2009 May;10(5):482-90.

REF 12

REF 13

Drug information of Methylscopolamine, 2008. eduDrugs.

REF 14

Clinical pipeline report, company report or official report of Summit.

REF 15

REF 16

FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 021518.

REF 17

REF 18

FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 008453.

REF 19

REF 20

ClinicalTrials.gov (NCT01458197) A Phase 2 Study to Compare the Efficacy and Tolerability of Tarafenacin 0.2 mg and Tarafenacin 0.4 mg to Placebo in Patients Suffering From Overactive Bladder.. U.S. National Institutes of Health.

REF 21

ClinicalTrials.gov (NCT02382510) Multiple Ascending Dose Study of TRN-157 in Stable Mild and Moderate Asthmatics. U.S. National Institutes of Health.

REF 22

Emerging drugs in chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2009 Mar;14(1):181-94.

REF 23

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003650)

REF 24

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022973)

REF 25

Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.

REF 26

In vivo muscarinic cholinergic mediated effects of Lu 25-109, a M1 agonist and M2/M3 antagonist in vitro. Psychopharmacology (Berl). 1998 Jun;137(3):233-40.

REF 27

Design, synthesis, and neurochemical evaluation of 5-(3-alkyl-1,2,4- oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidines as M1 muscarinic receptor agonists. J Med Chem. 1993 Apr 2;36(7):842-7.

REF 28

Degradation of submandibular gland AQP5 by parasympathetic denervation of chorda tympani and its recovery by cevimeline, an M3 muscarinic receptor ... Am J Physiol Gastrointest Liver Physiol. 2008 Jul;295(1):G112-G123.

REF 29

M(1) and M(3) muscarinic receptors are involved in the release of urinary bladder-derived relaxant factor. Pharmacol Res. 2009 May;59(5):300-5.

REF 30

Characterisation of [3H]-darifenacin as a novel radioligand for the study of muscarinic M3 receptors. J Recept Signal Transduct Res. 1997 Jan-May;17(1-3):177-84.

REF 31

Role of parasympathetic nerves and muscarinic receptors in allergy and asthma.Chem Immunol Allergy.2012;98:48-69.

REF 32

Muscarinic M3-receptors mediate cholinergic synergism of mitogenesis in airway smooth muscle. Am J Respir Cell Mol Biol. 2003 Feb;28(2):257-62.

REF 33

Agonist-regulated alteration of the affinity of pancreatic muscarinic cholinergic receptors. J Biol Chem. 1993 Oct 25;268(30):22436-43.

REF 34

Interaction of neuromuscular blocking drugs with recombinant human m1-m5 muscarinic receptors expressed in Chinese hamster ovary cells. Br J Pharmacol. 1998 Nov;125(5):1088-94.

REF 35

Demonstration of bladder selective muscarinic receptor binding by intravesical oxybutynin to treat overactive bladder. J Urol. 2004 Nov;172(5 Pt 1):2059-64.

REF 36

Comparison of muscarinic receptor selectivity of solifenacin and oxybutynin in the bladder and submandibular gland of muscarinic receptor knockout ... Eur J Pharmacol. 2009 Aug 1;615(1-3):201-6.

REF 37

The involvement of histaminic and muscarinic receptors in the bronchoconstriction induced by myorelaxant administration in sensitized rabbits. Anesth Analg. 2008 Dec;107(6):1899-906.

REF 38

Neuromuscular relaxants as antagonists for M2 and M3 muscarinic receptors. Anesthesiology. 1998 Mar;88(3):744-50.

REF 39

Pharmacological characterization of GSK573719 (umeclidinium): a novel, long-acting, inhaled antagonist of the muscarinic cholinergic receptors for treatment of pulmonary diseases. J Pharmacol Exp Ther. 2013 May;345(2):260-70.

REF 40

Signal transduction underlying carbachol-induced contraction of human urinary bladder. J Pharmacol Exp Ther. 2004 Jun;309(3):1148-53.

REF 41

Knockouts model the 100 best-selling drugs--will they model the next 100 Nat Rev Drug Discov. 2003 Jan;2(1):38-51.

REF 42

In vivo and in vitro pharmacological characterization of SVT-40776, a novel M3 muscarinic receptor antagonist, for the treatment of overactive bladder. Br J Pharmacol. 2009 Mar;156(5):807-17.

REF 43

REF 44

Bronchodilator activity of (3R)-3-[[[(3-fluorophenyl)[(3,4,5-trifluorophenyl)methyl]amino] carbonyl]oxy]-1-[2-oxo-2-(2-thienyl)ethyl]-1-azoniabicyc... J Pharmacol Exp Ther. 2010 Dec;335(3):622-35.

REF 45

Drug treatment options for irritable bowel syndrome: managing for success. Drugs Aging. 2001;18(3):201-11.

REF 46

Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.

REF 47

Discovery & development of selective M3 antagonists for clinical use.Life Sci.1997;60(13-14):1053-60.

REF 48

Synthesis and biological evaluation of [125I]- and [123I]-4-iododexetimide, a potent muscarinic cholinergic receptor antagonist. J Med Chem. 1989 May;32(5):1057-62.

REF 49

Discovery of (3-endo)-3-(2-cyano-2,2-diphenylethyl)-8,8-dimethyl-8-azoniabicyclo[3.2.1]octane bromide as an efficacious inhaled muscarinic acetylch... Bioorg Med Chem Lett. 2009 Aug 15;19(16):4560-2.

REF 50

Urea and 2-imidazolidone derivatives of the muscarinic agents oxotremorine and N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide. J Med Chem. 1992 Aug 21;35(17):3270-9.

REF 51

Synthesis and modeling studies of a potent conformationally rigid muscarinic agonist: 1-azabicyclo[2.2.1]heptanespirofuranone. J Med Chem. 1998 Oct 22;41(22):4181-5.

REF 52

Cholinergic agents: aldehyde, ketone, and oxime analogues of the muscarinic agonist UH5, Bioorg. Med. Chem. Lett. 2(8):803-808 (1992).

REF 53

Designing active template molecules by combining computational de novo design and human chemist's expertise. J Med Chem. 2007 Apr 19;50(8):1925-32.

REF 54

Synthesis and muscarinic activities of quinuclidin-3-yltriazole and -tetrazole derivatives. J Med Chem. 1992 Apr 3;35(7):1280-90.

REF 55

Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 rec... J Med Chem. 2010 Sep 9;53(17):6386-97.

REF 56

An increase in intracelluar free calcium ions modulated by cholinergic receptors in rat facial nucleus. Chin Med J (Engl). 2009 May 5;122(9):1049-55.

REF 57

The effects of the antagonists of muscarinic acetylcholine receptor subtypes in rat brain on urinary bladder contraction. Nippon Hinyokika Gakkai Zasshi. 2002 Mar;93(3):427-34.

REF 58

cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine (A-987306), a new histamine H4R antagonist that blocks pain... J Med Chem. 2008 Nov 27;51(22):7094-8.

REF 59

6beta-Acetoxynortropane: a potent muscarinic agonist with apparent selectivity toward M2-receptors. J Med Chem. 1998 Jun 4;41(12):2047-55.

REF 60

Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors. Mol Pharmacol. 1997 Jul;52(1):172-9.

REF 61

6beta-Acyloxy(nor)tropanes: affinities for antagonist/agonist binding sites on transfected and native muscarinic receptors. J Med Chem. 2000 Jun 29;43(13):2514-22.

REF 62

A novel and selective class of azabicyclic muscarinic agonists incorporating an N-methoxy imidoyl halide or nitrile functionality, Bioorg. Med. Chem. Lett. 2(8):791-796 (1992).

REF 63

Subtype-selective positive cooperative interactions between brucine analogues and acetylcholine at muscarinic receptors: radioligand binding studies. Mol Pharmacol. 1998 Mar;53(3):573-89.

REF 64

Cremastrine, a pyrrolizidine alkaloid from Cremastra appendiculata. J Nat Prod. 2005 Apr;68(4):572-3.

REF 65

Synthesis, absolute configuration, conformational analysis and binding affinity properties of enantiomeric forms of DAU 5750, a novel M1-M3 muscari... Bioorg Med Chem. 1994 Dec;2(12):1375-83.

REF 66

Doi: 10.1038/bjp.2008.208

REF 67

Synthesis and pharmacological evaluation of a series of 4-piperazinylpyrazolo[3,4-b]- and -[4,3-b][1,5]benzodiazepines as potential anxiolytics. J Med Chem. 1989 Dec;32(12):2573-82.

REF 68

Design and synthesis of a fluorescent muscarinic antagonist. Bioorg Med Chem Lett. 2008 Jan 15;18(2):825-7.

REF 69

Nocardimicins A, B, C, D, E, and F, siderophores with muscarinic M3 receptor inhibiting activity from Nocardia sp. TP-A0674. J Nat Prod. 2005 Jul;68(7):1061-5.

REF 70

Allosteric interactions of staurosporine and other indolocarbazoles with N-[methyl-(3)H]scopolamine and acetylcholine at muscarinic receptor subtypes: identification of a second allosteric site. Mol Pharmacol. 2000 Jul;58(1):194-207.

REF 71

Binding of the labelled muscarinic toxin 125I-MT1 to rat brain muscarinic M1 receptors. Eur J Pharmacol. 1996 Jun 3;305(1-3):187-92.

REF 72

Antagonist binding properties of five cloned muscarinic receptors expressed in CHO-K1 cells. Mol Pharmacol. 1989 Apr;35(4):469-76.

REF 73

Chloro-substituted, sterically hindered 5,11-dicarbo analogues of clozapine as potential chiral antipsychotic agents. J Med Chem. 1990 Feb;33(2):809-14.

REF 74

Synthesis of clozapine analogues and their affinity for clozapine and spiroperidol binding sites in rat brain. J Med Chem. 1981 Sep;24(9):1021-6.

REF 75

Lithocholylcholine, a bile acid/acetylcholine hybrid, is a muscarinic receptor antagonist. J Pharmacol Exp Ther. 2002 Oct;303(1):29-35.

REF 76

Human muscarinic receptors expressed in A9L and CHO cells: activation by full and partial agonists. Br J Pharmacol. 1995 Mar;114(6):1241-9.

REF 77

Discovery, synthesis and characterization of a highly muscarinic acetylcholine receptor (mAChR)-selective M5-orthosteric antagonist, VU0488130 (ML381): a novel molecular probe. ChemMedChem. 2014 Aug;9(8):1677-82.

REF 78

Synthesis and pharmacological evaluation of dimeric muscarinic acetylcholine receptor agonists. J Pharmacol Exp Ther. 2001 Sep;298(3):1260-8.

REF 79

Which muscarinic receptor is important in the bladder World J Urol. 2001 Nov;19(5):299-306.

REF 80

Generation of an agonistic binding site for blockers of the M(3) muscarinic acetylcholine receptor. Biochem J. 2008 May 15;412(1):103-12.

REF 81

Stimulation of cyclic AMP accumulation and phosphoinositide hydrolysis by M3 muscarinic receptors in the rat peripheral lung. Biochem Pharmacol. 1996 Aug 23;52(4):643-58.

REF 82

Heterocyclic muscarinic agonists. Synthesis and biological activity of some bicyclic sulfonium arecoline bioisosteres. J Med Chem. 1988 Jul;31(7):1312-6.

REF 83

Thiochrome enhances acetylcholine affinity at muscarinic M4 receptors: receptor subtype selectivity via cooperativity rather than affinity. Mol Pharmacol. 2004 Jan;65(1):257-66.

REF 84

Design, synthesis, and biological evaluation of pirenzepine analogs bearing a 1,2-cyclohexanediamine and perhydroquinoxaline units in exchange for the piperazine ring as antimuscarinics. Bioorg Med Chem. 2008 Aug 1;16(15):7311-20.

REF 85

Dual M3 antagonists-PDE4 inhibitors. Part 2: Synthesis and SAR of 3-substituted azetidinyl derivatives. Bioorg Med Chem Lett. 2007 Jun 1;17(11):3077-80.

REF 86

Comparison of the in vitro and in vivo profiles of tolterodine with those of subtype-selective muscarinic receptor antagonists. Eur J Pharmacol. 1998 May 22;349(2-3):285-92.

REF 87

A novel selective muscarinic acetylcholine receptor subtype 1 antagonist reduces seizures without impairing hippocampus-dependent learning. Mol Pharmacol. 2009 Aug;76(2):356-68.

REF 88

Analogs of WIN 62,577 define a second allosteric site on muscarinic receptors. Mol Pharmacol. 2002 Dec;62(6):1492-505.

REF 89

Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors. EMBO J. 1987 Dec 20;6(13):3923-9.

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