Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTQ13Z5)

• DTT Name: Muscarinic acetylcholine receptor M3 (CHRM3)
• Synonyms: M3 receptor; CHRM3
• Gene Name: CHRM3
• DTT Type: Successful target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: ACM3_HUMAN
• TTD ID: T67684
• Sequence:
  MTLHNNSTTSPLFPNISSSWIHSPSDAGLPPGTVTHFGSYNVSRAAGNFSSPDGTTDDPL
  GGHTVWQVVFIAFLTGILALVTIIGNILVIVSFKVNKQLKTVNNYFLLSLACADLIIGVI
  SMNLFTTYIIMNRWALGNLACDLWLAIDYVASNASVMNLLVISFDRYFSITRPLTYRAKR
  TTKRAGVMIGLAWVISFVLWAPAILFWQYFVGKRTVPPGECFIQFLSEPTITFGTAIAAF
  YMPVTIMTILYWRIYKETEKRTKELAGLQASGTEAETENFVHPTGSSRSCSSYELQQQSM
  KRSNRRKYGRCHFWFTTKSWKPSSEQMDQDHSSSDSWNNNDAAASLENSASSDEEDIGSE
  TRAIYSIVLKLPGHSTILNSTKLPSSDNLQVPEEELGMVDLERKADKLQAQKSVDDGGSF
  PKSFSKLPIQLESAVDTAKTSDVNSSVGKSTATLPLSFKEATLAKRFALKTRSQITKRKR
  MSLVKEKKAAQTLSAILLAFIITWTPYNIMVLVNTFCDSCIPKTFWNLGYWLCYINSTVN
  PVCYALCNKTFRTTFKMLLLCQCDKKKRRKQQYQQRQSVIFHKRAPEQAL
• 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.
• KEGG Pathway:
  Calcium signaling pathway (hsa04020)
  Neuroactive ligand-receptor interaction (hsa04080)
  Cholinergic synapse (hsa04725)
  Regulation of actin cytoskeleton (hsa04810)
  Insulin secretion (hsa04911)
  Salivary secretion (hsa04970)
  Gastric acid secretion (hsa04971)
  Pancreatic secretion (hsa04972)
• Reactome Pathway:
  Acetylcholine regulates insulin secretion (R-HSA-399997)
  G alpha (q) signalling events (R-HSA-416476)
  Muscarinic acetylcholine receptors (R-HSA-390648)

Molecular Interaction Atlas (MIA) of This DTT

13 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ACECLIDINE	DMOLNCZ	Glaucoma/ocular hypertension	9C61	Approved	[2]
Cevimeline	DMWSMND	Sjogren syndrome	4A43.20	Approved	[3]
Darifenacin	DMWXLYZ	Overactive bladder	GC50.0	Approved	[4]
Ipratropium	DMFQ320	Obstructive lung disease	CA22.Z	Approved	[5]
LAS-34273	DMSQ1JV	Chronic obstructive pulmonary disease	CA22	Approved	[6]
Methacholine Chloride	DMGS4QH	Asthma	CA23	Approved	[7]
Methscopolamine Bromide	DMHP8FI	Nausea and vomiting	MD90	Approved	[8]
Methylscopolamine	DM5VWOB	Peptic ulcer	DA61	Approved	[9]
SMT-D002	DM1I93C	Seborrhea	ED91.2	Approved	[10]
Solifenacin	DMG592Q	Overactive bladder	GC50.0	Approved	[11]
Succinylcholine	DM2ET1M	Plasma cell myeloma	2A83.1	Approved	[12]
Tiotropium	DMFDC0Q	Chronic obstructive pulmonary disease	CA22	Approved	[1]
Tolterodine	DMSHPW8	Overactive bladder	GC50.0	Approved	[13]

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tarafenacin	DMDB4EJ	Overactive bladder	GC50.0	Phase 2	[14]
TRN-157	DM64NYP	Chronic obstructive pulmonary disease	CA22	Phase 2	[15]
CHF 5407	DMSDNU1	Chronic obstructive pulmonary disease	CA22	Phase 1	[16]

4 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zamifenacin	DM51FVE	Urinary incontinence	MF50.2	Discontinued in Phase 3	[17]
PSD-506	DMT0KB1	Overactive bladder	GC50.0	Discontinued in Phase 2	[18]
Revatropate	DMT5VXF	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 1	[19]
Alvameline	DMLN0Y5	Alzheimer disease	8A20	Terminated	[20]

72 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1'-Benzyl-3-phenyl-[3,4']bipiperidinyl-2,6-dione	DMMNH4K	Discovery agent	N.A.	Investigative	[21]
1,1-diphenyl-2-(3-tropanyl)ethanol	DMZDUSA	Discovery agent	N.A.	Investigative	[22]
1-Methyl-1-(4-pyrrolidin-1-yl-but-2-ynyl)-urea	DM9KCXI	Discovery agent	N.A.	Investigative	[23]
2,8-Dimethyl-1-oxa-8-aza-spiro[4.5]decan-3-one	DMAKZ43	Discovery agent	N.A.	Investigative	[24]
2-Methyl-6-pyrrolidin-1-yl-hex-4-ynal oxime	DM8EV4A	Discovery agent	N.A.	Investigative	[25]
3-(1-carbamoyl-1,1-diphenylmethyl)-1-(4-methoxyphenylethyl)pyrrolidine (APP)	DMOMSTN	Discovery agent	N.A.	Investigative	[13]
3-(3-benzylamino)-piperidin-2-one	DMYN6Z9	Discovery agent	N.A.	Investigative	[26]
3-Methyl-7-pyrrolidin-1-yl-hept-5-yn-2-one	DME81U3	Discovery agent	N.A.	Investigative	[25]
3-Tetrazol-2-yl-1-aza-bicyclo[2.2.2]octane	DMIH6JU	Discovery agent	N.A.	Investigative	[27]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one	DMM9X0G	Discovery agent	N.A.	Investigative	[28]
4-DAMP	DMZIUQ2	Discovery agent	N.A.	Investigative	[29]
6-Dimethylamino-2-methyl-hex-4-ynal oxime	DML2AC1	Discovery agent	N.A.	Investigative	[25]
7-Dimethylamino-3-methyl-hept-5-yn-2-one	DMDY2PQ	Discovery agent	N.A.	Investigative	[25]
7-Dimethylamino-hept-5-yn-2-one	DMH782V	Discovery agent	N.A.	Investigative	[25]
7-Pyrrolidin-1-yl-hept-5-yn-2-one	DMQJ26K	Discovery agent	N.A.	Investigative	[25]
A-987306	DMU34BK	Discovery agent	N.A.	Investigative	[30]
Acetic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester	DMVEH40	Discovery agent	N.A.	Investigative	[31]
AE-9C90CB	DMANEH2	Overactive bladder	GC50.0	Investigative	[15]
arecaidine propargyl ester	DMSA6IY	Discovery agent	N.A.	Investigative	[32]
Benzoic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester	DM6T8YM	Discovery agent	N.A.	Investigative	[33]
BRL-55473	DMEMZ6Q	Discovery agent	N.A.	Investigative	[34]
brucine	DM50RUD	Discovery agent	N.A.	Investigative	[35]
Cremastrine	DMLJOGK	Discovery agent	N.A.	Investigative	[36]
DAU-5750	DMT14A7	Discovery agent	N.A.	Investigative	[37]
DAU-5884	DMEZVGK	Discovery agent	N.A.	Investigative	[38]
FLUMEZAPINE	DMW0HOG	Discovery agent	N.A.	Investigative	[39]
FM1-10	DM5782Z	Discovery agent	N.A.	Investigative	[40]
FM1-43	DMAP8VY	Discovery agent	N.A.	Investigative	[40]
furtrethonium	DM4M3C8	Discovery agent	N.A.	Investigative	[32]
GNF-PF-5618	DMT8VUS	Discovery agent	N.A.	Investigative	[41]
Go7874	DMS91OR	Discovery agent	N.A.	Investigative	[42]
guanylpirenzepine	DMOUQLB	Discovery agent	N.A.	Investigative	[43]
hexahydrodifenidol	DMH25OD	Discovery agent	N.A.	Investigative	[44]
hexahydrosiladifenidol	DM6UAV7	Discovery agent	N.A.	Investigative	[44]
ISOCLOZAPINE	DM52CPU	Discovery agent	N.A.	Investigative	[45]
ISOLOXAPINE	DMH1BN4	Discovery agent	N.A.	Investigative	[46]
J-104135	DMAEQS9	Chronic obstructive pulmonary disease	CA22	Investigative	[15]
lithocholylcholine	DME76CQ	Discovery agent	N.A.	Investigative	[47]
McN-A-343	DML3AZG	Discovery agent	N.A.	Investigative	[48]
methylfurmethide	DMZ318I	Discovery agent	N.A.	Investigative	[32]
ML381	DMKCIP0	Discovery agent	N.A.	Investigative	[49]
N-(4-Dimethylamino-but-2-ynyl)-N-methyl-acetamide	DMB3E7H	Discovery agent	N.A.	Investigative	[25]
N-benzyl brucine	DMOQMEU	Discovery agent	N.A.	Investigative	[35]
N-chloromethyl-brucine	DM6VEON	Discovery agent	N.A.	Investigative	[35]
N-methoxyquinuclidine-3-carboximidoyl chloride	DMMB3PG	Discovery agent	N.A.	Investigative	[34]
N-methoxyquinuclidine-3-carboximidoyl fluoride	DMF8IA6	Discovery agent	N.A.	Investigative	[34]
NNC 11-1314	DMSQ4TL	Discovery agent	N.A.	Investigative	[50]
NNC 11-1585	DMMX19B	Discovery agent	N.A.	Investigative	[50]
NNC 11-1607	DMZJSWI	Discovery agent	N.A.	Investigative	[50]
NOCARDIMICIN A	DMN7GO8	Discovery agent	N.A.	Investigative	[41]
Nocardimicin C	DM4SRL7	Discovery agent	N.A.	Investigative	[41]
Nocardimicin D	DM1SABZ	Discovery agent	N.A.	Investigative	[41]
Nocardimicin F	DMK02YC	Discovery agent	N.A.	Investigative	[41]
Noccardimicin E	DMXOF4Z	Discovery agent	N.A.	Investigative	[41]
Olterodine	DMTY63G	Discovery agent	N.A.	Investigative	[51]
Oxybutynine	DMJPBAX	Obsolete neurogenic bladder		Investigative	[52]
p-F-HHSiD	DM9CV6S	Discovery agent	N.A.	Investigative	[53]
pentylthio-TZTP	DMD8NHB	Discovery agent	N.A.	Investigative	[32]
Propionic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester	DMO325J	Discovery agent	N.A.	Investigative	[33]
PTAC	DMEJ6SK	Discovery agent	N.A.	Investigative	[51]
silahexocyclium	DM4VDMP	Discovery agent	N.A.	Investigative	[44]
SULFOARECOLINE	DM8KYUE	Discovery agent	N.A.	Investigative	[54]
thiochrome	DML4TQ5	Discovery agent	N.A.	Investigative	[55]
tripitramine	DMWZ5FB	Discovery agent	N.A.	Investigative	[56]
UCB-101333-3	DMHYORU	Discovery agent	N.A.	Investigative	[57]
UH-AH 37	DMT5UMG	Discovery agent	N.A.	Investigative	[58]
vinburnine	DMO4GBK	Discovery agent	N.A.	Investigative	[32]
VU0255035	DMRKE6W	Discovery agent	N.A.	Investigative	[59]
WIN 51,708	DMY5LOB	Discovery agent	N.A.	Investigative	[60]
WIN 62,577	DMGOQY2	Discovery agent	N.A.	Investigative	[60]
[3H]oxotremorine-M	DM5L7D3	Discovery agent	N.A.	Investigative	[32]
[3H]QNB	DMC1WHR	Discovery agent	N.A.	Investigative	[61]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Alzheimer's disease	8A00.0	Entorhinal cortex	4.61E-07	-0.59	-0.73
Sjogren's syndrome	4A43.2	Salivary gland tissue	3.56E-01	-0.25	-0.73
Chronic obstructive pulmonary disease	CA23	Lung tissue	2.09E-01	-0.04	-0.11
Chronic obstructive pulmonary disease	CA23	Small airway epithelium	1.52E-02	-0.06	-0.39
Schizophrenia	6A20	Pre-frontal cortex	8.42E-02	-0.38	-0.24
Schizophrenia	6A20	Superior temporal cortex	2.55E-01	0.14	0.37

References

• [1] DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] Role of parasympathetic nerves and muscarinic receptors in allergy and asthma.Chem Immunol Allergy.2012;98:48-69.
• [6] Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
• [7] Muscarinic M3-receptors mediate cholinergic synergism of mitogenesis in airway smooth muscle. Am J Respir Cell Mol Biol. 2003 Feb;28(2):257-62.
• [8] Agonist-regulated alteration of the affinity of pancreatic muscarinic cholinergic receptors. J Biol Chem. 1993 Oct 25;268(30):22436-43.
• [9] 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.
• [10] Demonstration of bladder selective muscarinic receptor binding by intravesical oxybutynin to treat overactive bladder. J Urol. 2004 Nov;172(5 Pt 1):2059-64.
• [11] 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.
• [12] 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.
• [13] Signal transduction underlying carbachol-induced contraction of human urinary bladder. J Pharmacol Exp Ther. 2004 Jun;309(3):1148-53.
• [14] 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.
• [15] 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. (Target id: 15).
• [16] 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.
• [17] Drug treatment options for irritable bowel syndrome: managing for success. Drugs Aging. 2001;18(3):201-11.
• [18] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [19] Discovery & development of selective M3 antagonists for clinical use.Life Sci.1997;60(13-14):1053-60.
• [20] 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.
• [21] 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.
• [22] 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.
• [23] 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.
• [24] 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.
• [25] Cholinergic agents: aldehyde, ketone, and oxime analogues of the muscarinic agonist UH5, Bioorg. Med. Chem. Lett. 2(8):803-808 (1992).
• [26] 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.
• [27] Synthesis and muscarinic activities of quinuclidin-3-yltriazole and -tetrazole derivatives. J Med Chem. 1992 Apr 3;35(7):1280-90.
• [28] 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.
• [29] 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.
• [30] 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.
• [31] 6beta-Acetoxynortropane: a potent muscarinic agonist with apparent selectivity toward M2-receptors. J Med Chem. 1998 Jun 4;41(12):2047-55.
• [32] Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors. Mol Pharmacol. 1997 Jul;52(1):172-9.
• [33] 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.
• [34] 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).
• [35] Subtype-selective positive cooperative interactions between brucine analogues and acetylcholine at muscarinic receptors: radioligand binding studies. Mol Pharmacol. 1998 Mar;53(3):573-89.
• [36] Cremastrine, a pyrrolizidine alkaloid from Cremastra appendiculata. J Nat Prod. 2005 Apr;68(4):572-3.
• [37] 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.
• [38] Doi: 10.1038/bjp.2008.208
• [39] 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.
• [40] Design and synthesis of a fluorescent muscarinic antagonist. Bioorg Med Chem Lett. 2008 Jan 15;18(2):825-7.
• [41] 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.
• [42] 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.
• [43] 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.
• [44] Antagonist binding properties of five cloned muscarinic receptors expressed in CHO-K1 cells. Mol Pharmacol. 1989 Apr;35(4):469-76.
• [45] Chloro-substituted, sterically hindered 5,11-dicarbo analogues of clozapine as potential chiral antipsychotic agents. J Med Chem. 1990 Feb;33(2):809-14.
• [46] 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.
• [47] Lithocholylcholine, a bile acid/acetylcholine hybrid, is a muscarinic receptor antagonist. J Pharmacol Exp Ther. 2002 Oct;303(1):29-35.
• [48] Human muscarinic receptors expressed in A9L and CHO cells: activation by full and partial agonists. Br J Pharmacol. 1995 Mar;114(6):1241-9.
• [49] 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.
• [50] Synthesis and pharmacological evaluation of dimeric muscarinic acetylcholine receptor agonists. J Pharmacol Exp Ther. 2001 Sep;298(3):1260-8.
• [51] Which muscarinic receptor is important in the bladder World J Urol. 2001 Nov;19(5):299-306.
• [52] Generation of an agonistic binding site for blockers of the M(3) muscarinic acetylcholine receptor. Biochem J. 2008 May 15;412(1):103-12.
• [53] 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.
• [54] Heterocyclic muscarinic agonists. Synthesis and biological activity of some bicyclic sulfonium arecoline bioisosteres. J Med Chem. 1988 Jul;31(7):1312-6.
• [55] Thiochrome enhances acetylcholine affinity at muscarinic M4 receptors: receptor subtype selectivity via cooperativity rather than affinity. Mol Pharmacol. 2004 Jan;65(1):257-66.
• [56] 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.
• [57] 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.
• [58] 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.
• [59] A novel selective muscarinic acetylcholine receptor subtype 1 antagonist reduces seizures without impairing hippocampus-dependent learning. Mol Pharmacol. 2009 Aug;76(2):356-68.
• [60] Analogs of WIN 62,577 define a second allosteric site on muscarinic receptors. Mol Pharmacol. 2002 Dec;62(6):1492-505.
• [61] 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.