Details of the Drug-Related molecule(s) Interaction Atlas

General Information of DTT (ID: TTH18TF)

• DTT Name: Muscarinic acetylcholine receptor M5 (CHRM5) DTT Info
• Gene Name: CHRM5

Molecule-Related Drug & Molecule List

31 Approved Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ACECLIDINE	DMOLNCZ	Glaucoma/ocular hypertension	9C61	Approved	[1]
Anisodine	DMNOSWU	Central and peripheral nervous disease	8A04-8E7Z	Approved	[2]
Anisotropine Methylbromide	DMIJRF0	Gastric ulcer	DA60	Approved	[3]
Atropine	DMEN6X7	Organophosphate poisoning	NE6Z	Approved	[4]
Belladonna	DM2RBWK	Colitis	1A40.Z	Approved	[5]
Bethanechol	DMCLHO0	Urinary retention	MF50.3	Approved	[6]
Butylscopolamine	DMZKXB7	Dysmenorrhea	GA34.3	Approved	[7]
Choline alfoscerate	DMOI1ZF	Amnesia	MB21.1	Approved	[8]
Cimetropium bromide	DMZHPNE	Gastric motility disorder	DA21	Approved	[9]
Cryptenamine Acetates	DMHCTAL	Hypertension	BA00-BA04	Approved	[10]
Cyclopentolate	DMA8LM5	Examination of eyes or vision	QA00.6	Approved	[11]
Emepronium	DMCOAVT	Urinary incontinence	MF50.2	Approved	[12]
Flavoxate	DMKV4NL	Dysuria	MF50.7	Approved	[13]
Flutropium bromide	DMU54C3	Cough	MD12	Approved	[9]
Homatropine Methylbromide	DMGBPSH	Cough	MD12	Approved	[14]
Hyoscyamine	DM804UR	Dysuria	MF50.7	Approved	[15]
Ispaghula	DMWCRN1	Irritable bowel syndrome	DD91.0	Approved	[16]
Mebeverine	DMNOBFQ	Irritable bowel syndrome	DD91.0	Approved	[16]
Mepenzolate	DM8YU2F	Gastric ulcer	DA60	Approved	[17]
Methantheline	DM8X4A1	Gastric ulcer	DA60	Approved	[18]
Oxitropium bromide	DM9FKSR	Asthma	CA23	Approved	[9]
Oxyphencyclimine	DM3TABW	Peptic ulcer	DA61	Approved	[19]
Pilocarpine	DMV9ADG	Glaucoma/ocular hypertension	9C61	Approved	[20]
Pramiracetam	DM2FHG3	Brain disease	8C70-8E61	Approved (orphan drug)	[21]
Prifinium	DMMZB0K	Irritable bowel syndrome	DD91.0	Approved	[22]
Procyclidine	DMHFJDT	Parkinson disease	8A00.0	Approved	[23]
Promazine	DMZAL7W	Acute intermittent hepatic porphyria	5C58.11	Approved	[24]
Propiverine	DMUWBIJ	Urinary incontinence	MF50.2	Approved	[25]
Tridihexethyl	DMVLHNI	Acquired nystagmus	9C84	Approved	[26]
Trospium	DMX6RTG	Overactive bladder	GC50.0	Approved	[14]
Umeclidinium	DM4E8O9	Chronic obstructive pulmonary disease	CA22	Approved	[27]

4 Clinical Trial Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-651582	DMWTPCA	Solid tumour/cancer	2A00-2F9Z	Phase 3	[28]
OrM3	DMEARCM	Chronic obstructive pulmonary disease	CA22	Phase 2b	[29]
GSK233705	DMXUCG3	Chronic obstructive pulmonary disease	CA22	Phase 2	[29]
Dexpirronium	DMAE9I0	Chronic obstructive pulmonary disease	CA22	Phase 1	[8]

7 Discontinued Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Benactyzine	DM0J92L	Depression	6A70-6A7Z	Withdrawn from market	[30]
BMS-181168	DMGPHTJ	Cognitive impairment	6D71	Discontinued in Phase 2	[31]
DDP-200	DMMV6RK	Urinary incontinence	MF50.2	Discontinued in Phase 2	[32]
FK-584	DMR2FPO	Central and peripheral nervous disease	8A04-8E7Z	Discontinued in Phase 2	[33]
AM-831	DMO7920	Schizophrenia	6A20	Discontinued in Phase 1	[34]
RS 86	DMKQV9A	Alzheimer disease	8A20	Terminated	[36]
SU-740	DMWCR1Z	Stomach ulcer	DA60.Z	Terminated	[37]

1 Preclinical Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Org-23366	DMHQUM2	Schizophrenia	6A20	Preclinical	[35]

42 Investigative Drug(s) Transported by This DTP

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	[38]
1-Methyl-1-(4-pyrrolidin-1-yl-but-2-ynyl)-urea	DM9KCXI	Discovery agent	N.A.	Investigative	[39]
2,8-Dimethyl-1-oxa-8-aza-spiro[4.5]decan-3-one	DMAKZ43	Discovery agent	N.A.	Investigative	[40]
2-Methyl-6-pyrrolidin-1-yl-hex-4-ynal oxime	DM8EV4A	Discovery agent	N.A.	Investigative	[41]
3-(3-benzylamino)-piperidin-2-one	DMYN6Z9	Discovery agent	N.A.	Investigative	[42]
3-Methyl-7-pyrrolidin-1-yl-hept-5-yn-2-one	DME81U3	Discovery agent	N.A.	Investigative	[41]
3-Tetrazol-2-yl-1-aza-bicyclo[2.2.2]octane	DMIH6JU	Discovery agent	N.A.	Investigative	[43]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one	DMM9X0G	Discovery agent	N.A.	Investigative	[44]
6-Dimethylamino-2-methyl-hex-4-ynal oxime	DML2AC1	Discovery agent	N.A.	Investigative	[41]
7-Dimethylamino-3-methyl-hept-5-yn-2-one	DMDY2PQ	Discovery agent	N.A.	Investigative	[41]
7-Dimethylamino-hept-5-yn-2-one	DMH782V	Discovery agent	N.A.	Investigative	[41]
7-Pyrrolidin-1-yl-hept-5-yn-2-one	DMQJ26K	Discovery agent	N.A.	Investigative	[41]
A-867744	DM96F8U	Discovery agent	N.A.	Investigative	[45]
Acetic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester	DMVEH40	Discovery agent	N.A.	Investigative	[46]
alpha-conotoxin AuIB	DM96EJ1	Discovery agent	N.A.	Investigative	[8]
alpha-conotoxin GI	DMHO634	Discovery agent	N.A.	Investigative	[8]
alpha-conotoxin PnIA	DM1QOY0	Discovery agent	N.A.	Investigative	[8]
Aprophen	DM0VBUL	Discovery agent	N.A.	Investigative	[30]
Benzoic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester	DM6T8YM	Discovery agent	N.A.	Investigative	[46]
BHT-3034	DMZRS7A	Myasthenia gravis	8C6Y	Investigative	[8]
BRL-55473	DMEMZ6Q	Discovery agent	N.A.	Investigative	[47]
Cremastrine	DMLJOGK	Discovery agent	N.A.	Investigative	[48]
CRTX-070	DMBV79R	Allergic rhinitis	CA08.0	Investigative	[8]
FLUMEZAPINE	DMW0HOG	Discovery agent	N.A.	Investigative	[49]
FM1-10	DM5782Z	Discovery agent	N.A.	Investigative	[50]
FM1-43	DMAP8VY	Discovery agent	N.A.	Investigative	[50]
GNF-PF-5618	DMT8VUS	Discovery agent	N.A.	Investigative	[51]
ISOCLOZAPINE	DM52CPU	Discovery agent	N.A.	Investigative	[52]
ISOLOXAPINE	DMH1BN4	Discovery agent	N.A.	Investigative	[53]
JWB-1-84-1	DMXZ9RF	Neurological disorder	6B60	Investigative	[8]
Muscarine	DMNDUJ5	Discovery agent	N.A.	Investigative	[54]
N-(4-Dimethylamino-but-2-ynyl)-N-methyl-acetamide	DMB3E7H	Discovery agent	N.A.	Investigative	[41]
N-methoxyquinuclidine-3-carboximidoyl chloride	DMMB3PG	Discovery agent	N.A.	Investigative	[47]
N-methoxyquinuclidine-3-carboximidoyl fluoride	DMF8IA6	Discovery agent	N.A.	Investigative	[47]
NS1738	DM2S5ZF	Discovery agent	N.A.	Investigative	[55]
PF-3409409	DMEZA0T	Attention deficit hyperactivity disorder	6A05.Z	Investigative	[56]
Recombinant botulinum toxin	DMA6VCG	Neurological disorder	6B60	Investigative	[8]
SULFOARECOLINE	DM8KYUE	Discovery agent	N.A.	Investigative	[57]
VU0119498	DMPSI10	Discovery agent	N.A.	Investigative	[58]
VU0238429	DMOPLQI	Discovery agent	N.A.	Investigative	[58]
[125I]epibatidine	DMZWQH3	Discovery agent	N.A.	Investigative	[8]
[3H]cytisine	DMVLRHW	Discovery agent	N.A.	Investigative	[8]

References

• [1] 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.
• [2] Medicinal plants in therapy. Bull World Health Organ. 1985;63(6):965-81.
• [3] Anisotropine methylbromide: a new antispasmodic for gastrointestinal disorders. Curr Ther Res Clin Exp. 1963 May;5:213-8.
• [4] Additive protective effects of donepezil and nicotine against salsolinol-induced cytotoxicity in SH-SY5Y cells. Neurotox Res. 2009 Oct;16(3):194-204.
• [5] Plasma level of atropine after accidental ingestion of Atropa belladonna. Clin Toxicol (Phila). 2009 Jul;47(6):602-4.
• [6] Loss of Ca-mediated ion transport during colitis correlates with reduced ion transport responses to a Ca-activated K channel opener. Br J Pharmacol. 2009 Apr;156(7):1085-97.
• [7] Comparison of pharmacological effects of L- and DL-n-butyl-scopolamine in rat uterus. Yao Xue Xue Bao. 1994;29(1):24-7.
• [8] 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: 467).
• [9] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [10] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [11] High spatial resolution studies of muscarinic neuroeffector junctions in mouse isolated vas deferens. Neuroscience. 2009 Sep 15;162(4):1366-76.
• [12] Classification of the presynaptic muscarinic receptor subtype that regulates 3H-acetylcholine secretion in the guinea pig urinary bladder in vitro. J Pharmacol Exp Ther. 1995 Jul;274(1):458-68.
• [13] Brain pertussis toxin-sensitive G proteins are involved in the flavoxate hydrochloride-induced suppression of the micturition reflex in rats. Brain Res. 1996 Jul 15;727(1-2):91-8.
• [14] Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34.
• [15] Reconstitution of the purified porcine atrial muscarinic acetylcholine receptor with purified porcine atrial inhibitory guanine nucleotide binding protein. Biochemistry. 1987 Dec 15;26(25):8175-82.
• [16] Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313.
• [17] Isolation of cholinergic active ingredients in aqueous extracts of Mareya micrantha using the longitudinal muscle of isolated guinea-pig ileum as a pharmacological activity marker. J Ethnopharmacol. 1995 Mar;45(3):215-22.
• [18] Anticholinergics for urinary symptoms in multiple sclerosis. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD004193.
• [19] Stereoselective interaction of procyclidine, hexahydro-difenidol, hexbutinol and oxyphencyclimine, and of related antagonists, with four muscarinic receptors. Eur J Pharmacol. 1992 Sep 1;227(1):33-42.
• [20] Retinoic acid prevents virus-induced airway hyperreactivity and M2 receptor dysfunction via anti-inflammatory and antiviral effects. Am J Physiol Lung Cell Mol Physiol. 2009 Aug;297(2):L340-6.
• [21] Some neurochemical properties of pramiracetam (CI-879), a new cognition-enhancing agent. Article first published online: 5 OCT 2004.
• [22] Ligand binding properties of muscarinic acetylcholine receptor subtypes (m1-m5) expressed in baculovirus-infected insect cells. J Pharmacol Exp Ther. 1995 Jul;274(1):378-84.
• [23] Protection against soman-induced seizures in rats: relationship among doses of prophylactics, soman, and adjuncts. Toxicol Appl Pharmacol. 2004 May 1;196(3):327-36.
• [24] Muscarinic cholinergic and histamine H1 receptor binding of phenothiazine drug metabolites. Life Sci. 1988;43(5):405-12.
• [25] Affinity profiles of various muscarinic antagonists for cloned human muscarinic acetylcholine receptor (mAChR) subtypes and mAChRs in rat heart and submandibular gland. Life Sci. 1999;64(25):2351-8.
• [26] Effect of anticholinergic agents upon acquired nystagmus: a double-blind study of trihexyphenidyl and tridihexethyl chloride. Neurology. 1991 Nov;41(11):1737-41.
• [27] 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: 7354).
• [28] The antiproliferative and antimetastatic compound L651582 inhibits muscarinic acetylcholine receptor-stimulated calcium influx and arachidonic acid release. J Pharmacol Exp Ther. 1991 Jun;257(3):967-71.
• [29] Emerging drugs in chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2009 Mar;14(1):181-94.
• [30] The muscarinic antagonists aprophen and benactyzine are noncompetitive inhibitors of the nicotinic acetylcholine receptor. Mol Pharmacol. 1987 Nov;32(5):678-85.
• [31] Efficacy and safety of BMY 21,502 in Alzheimer disease. Ann Pharmacother. 1996 Dec;30(12):1376-80.
• [32] CA patent application no. 753057, Sustained release oral dosage forms of an r-baclofen prodrug.
• [33] US patent application no. 2005,0261,328, Pharmaceutical composition comprising beta-3-adrenoceptor-agonists and antimuscarinic agents.
• [34] Clinical pipeline report, company report or official report of Avarx.
• [35] The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
• [36] The pharmacological assessment of RS 86 (2-ethyl-8-methyl-2,8-diazaspiro-[4,5]-decan-1,3-dion hydrobromide). A potent, specific muscarinic acetylcholine receptor agonist. Eur J Pharmacol. 1986 Jun 5;125(1):45-62.
• [37] SU-840, a novel synthetic flavonoid derivative of sophoradin, with potent gastroprotective and ulcer healing activity. Journal of physiology and pharmacology. 49:1 1998 Mar pg 83-98
• [38] 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.
• [39] 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.
• [40] 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.
• [41] Cholinergic agents: aldehyde, ketone, and oxime analogues of the muscarinic agonist UH5, Bioorg. Med. Chem. Lett. 2(8):803-808 (1992).
• [42] 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.
• [43] Synthesis and muscarinic activities of quinuclidin-3-yltriazole and -tetrazole derivatives. J Med Chem. 1992 Apr 3;35(7):1280-90.
• [44] 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.
• [45] In vitro pharmacological characterization of a novel allosteric modulator of alpha 7 neuronal acetylcholine receptor, 4-(5-(4-chlorophenyl)-2-methy... J Pharmacol Exp Ther. 2009 Jul;330(1):257-67.
• [46] 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.
• [47] 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).
• [48] Cremastrine, a pyrrolizidine alkaloid from Cremastra appendiculata. J Nat Prod. 2005 Apr;68(4):572-3.
• [49] 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.
• [50] Design and synthesis of a fluorescent muscarinic antagonist. Bioorg Med Chem Lett. 2008 Jan 15;18(2):825-7.
• [51] 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.
• [52] Chloro-substituted, sterically hindered 5,11-dicarbo analogues of clozapine as potential chiral antipsychotic agents. J Med Chem. 1990 Feb;33(2):809-14.
• [53] 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.
• [54] 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.
• [55] An allosteric modulator of the alpha7 nicotinic acetylcholine receptor possessing cognition-enhancing properties in vivo. J Pharmacol Exp Ther. 2007 Oct;323(1):294-307.
• [56] Design, synthesis and evaluation of N-[(3S)-pyrrolidin-3-yl]benzamides as selective noradrenaline reuptake inhibitors: CNS penetration in a more po... Bioorg Med Chem Lett. 2009 Aug 15;19(16):4579-83.
• [57] Heterocyclic muscarinic agonists. Synthesis and biological activity of some bicyclic sulfonium arecoline bioisosteres. J Med Chem. 1988 Jul;31(7):1312-6.
• [58] Discovery of the first highly M5-preferring muscarinic acetylcholine receptor ligand, an M5 positive allosteric modulator derived from a series of ... J Med Chem. 2009 Jun 11;52(11):3445-8.