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

General Information of Drug (ID: DMIH6JU)

• Drug Name: 3-Tetrazol-2-yl-1-aza-bicyclo[2.2.2]octane Drug Info
• Synonyms: CHEMBL23563; SCHEMBL8430767; AMJXIOSRIOJUEM-UHFFFAOYSA-N; BDBM50229667

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 15663667
  TTD Drug ID: DMIH6JU

Molecule-Related Drug Atlas

Drug(s) Targeting Muscarinic acetylcholine receptor M4 (CHRM4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ACECLIDINE	DMOLNCZ	Glaucoma/ocular hypertension	9C61	Approved	[2]
Methacholine Chloride	DMGS4QH	Asthma	CA23	Approved	[3]
Tropicamide	DM1D90W	Mydriasis	LA11.62	Approved	[4]
Diphenidol	DMHPWOM	Nausea	MD90	Approved	[5]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one	DMM9X0G	Discovery agent	N.A.	Investigative	[6]
A-987306	DMU34BK	Discovery agent	N.A.	Investigative	[7]
ISOCLOZAPINE	DM52CPU	Discovery agent	N.A.	Investigative	[8]
FLUMEZAPINE	DMW0HOG	Discovery agent	N.A.	Investigative	[9]
ISOLOXAPINE	DMH1BN4	Discovery agent	N.A.	Investigative	[10]
Acetic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester	DMVEH40	Discovery agent	N.A.	Investigative	[3]

Drug(s) Targeting Muscarinic acetylcholine receptor M1 (CHRM1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ACECLIDINE	DMOLNCZ	Glaucoma/ocular hypertension	9C61	Approved	[2]
Fesoterodine fumarate	DM13495	Overactive bladder	GC50.0	Approved	[11]
SMT-D002	DM1I93C	Seborrhea	ED91.2	Approved	[12]
Clidinium	DMUMQZ0	Abdominal stomach pain	DD91.4	Approved	[13]
Trihexyphenidyl	DMB19L8	Dystonia	8A02	Approved	[14]
Oxyphenonium	DMMQHOZ	Visceral spasms	MD81.4	Approved	[15]
Benztropine	DMGZOVN	Parkinson disease	8A00.0	Approved	[16]
Glycopyrrolate	DM2M3ZA	Anaesthesia	9A78.6	Approved	[17]
Pirenzepine	DMP6M1N	Peptic ulcer	DA61	Approved	[18]
Cycrimine	DM8C43Q	Parkinson disease	8A00.0	Approved	[19]

Drug(s) Targeting Muscarinic acetylcholine receptor M2 (CHRM2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ACECLIDINE	DMOLNCZ	Glaucoma/ocular hypertension	9C61	Approved	[2]
Methacholine Chloride	DMGS4QH	Asthma	CA23	Approved	[3]
SMT-D002	DM1I93C	Seborrhea	ED91.2	Approved	[12]
Methylscopolamine	DM5VWOB	Peptic ulcer	DA61	Approved	[20]
Gallamine Triethiodide	DMPO0MS	Stabilize muscle contraction	FB3Z	Approved	[21]
FP-1097	DMC1F2T	Urinary incontinence	MF50.2	Phase 2	[22]
PSD-506	DMT0KB1	Overactive bladder	GC50.0	Discontinued in Phase 2	[23]
Otenzepad	DMRXHAC	Heart failure	BD10-BD13	Discontinued in Phase 2	[24]
SCH-211803	DM92E0W	Parkinson disease	8A00.0	Discontinued in Phase 1	[25]
Alvameline	DMLN0Y5	Alzheimer disease	8A20	Terminated	[26]

Drug(s) Targeting Muscarinic acetylcholine receptor M3 (CHRM3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tolterodine	DMSHPW8	Overactive bladder	GC50.0	Approved	[27]
ACECLIDINE	DMOLNCZ	Glaucoma/ocular hypertension	9C61	Approved	[2]
Tiotropium	DMFDC0Q	Chronic obstructive pulmonary disease	CA22	Approved	[28]
Ipratropium	DMFQ320	Obstructive lung disease	CA22.Z	Approved	[29]
Darifenacin	DMWXLYZ	Overactive bladder	GC50.0	Approved	[30]
Methacholine Chloride	DMGS4QH	Asthma	CA23	Approved	[31]
SMT-D002	DM1I93C	Seborrhea	ED91.2	Approved	[12]
Solifenacin	DMG592Q	Overactive bladder	GC50.0	Approved	[32]
Methylscopolamine	DM5VWOB	Peptic ulcer	DA61	Approved	[33]
Cevimeline	DMWSMND	Sjogren syndrome	4A43.20	Approved	[34]

Drug(s) Targeting Muscarinic acetylcholine receptor M5 (CHRM5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Promazine	DMZAL7W	Acute intermittent hepatic porphyria	5C58.11	Approved	[35]
ACECLIDINE	DMOLNCZ	Glaucoma/ocular hypertension	9C61	Approved	[2]
Pilocarpine	DMV9ADG	Glaucoma/ocular hypertension	9C61	Approved	[36]
Anisodine	DMNOSWU	Central and peripheral nervous disease	8A04-8E7Z	Approved	[37]
Atropine	DMEN6X7	Organophosphate poisoning	NE6Z	Approved	[38]
Propiverine	DMUWBIJ	Urinary incontinence	MF50.2	Approved	[39]
Umeclidinium	DM4E8O9	Chronic obstructive pulmonary disease	CA22	Approved	[40]
Cimetropium bromide	DMZHPNE	Gastric motility disorder	DA21	Approved	[41]
Butylscopolamine	DMZKXB7	Dysmenorrhea	GA34.3	Approved	[42]
Trospium	DMX6RTG	Overactive bladder	GC50.0	Approved	[43]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Muscarinic acetylcholine receptor M1 (CHRM1)	TTZ9SOR	ACM1_HUMAN	Inhibitor	[1]
Muscarinic acetylcholine receptor M2 (CHRM2)	TTYEG6Q	ACM2_HUMAN	Inhibitor	[1]
Muscarinic acetylcholine receptor M3 (CHRM3)	TTQ13Z5	ACM3_HUMAN	Inhibitor	[1]
Muscarinic acetylcholine receptor M4 (CHRM4)	TTQ3JTF	ACM4_HUMAN	Inhibitor	[1]
Muscarinic acetylcholine receptor M5 (CHRM5)	TTH18TF	ACM5_HUMAN	Inhibitor	[1]

References

• [1] Synthesis and muscarinic activities of quinuclidin-3-yltriazole and -tetrazole derivatives. J Med Chem. 1992 Apr 3;35(7):1280-90.
• [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] 6beta-Acetoxynortropane: a potent muscarinic agonist with apparent selectivity toward M2-receptors. J Med Chem. 1998 Jun 4;41(12):2047-55.
• [4] The muscarinic receptor antagonist tropicamide suppresses tremulous jaw movements in a rodent model of parkinsonian tremor: possible role of M4 rec... Psychopharmacology (Berl). 2007 Oct;194(3):347-59.
• [5] Diphenidol-related diamines as novel muscarinic M4 receptor antagonists. Bioorg Med Chem Lett. 2008 May 1;18(9):2972-6.
• [6] 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.
• [7] 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.
• [8] Chloro-substituted, sterically hindered 5,11-dicarbo analogues of clozapine as potential chiral antipsychotic agents. J Med Chem. 1990 Feb;33(2):809-14.
• [9] 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.
• [10] 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.
• [11] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [12] Demonstration of bladder selective muscarinic receptor binding by intravesical oxybutynin to treat overactive bladder. J Urol. 2004 Nov;172(5 Pt 1):2059-64.
• [13] Accidental acute clidinium toxicity. Emerg Med J. 2009 Jun;26(6):460.
• [14] The role of M1 muscarinic cholinergic receptors in the discriminative stimulus properties of N-desmethylclozapine and the atypical antipsychotic dr... Psychopharmacology (Berl). 2009 Apr;203(2):295-301.
• [15] Ultraviolet spectroscopic estimation of microenvironments and bitter tastes of oxyphenonium bromide in cyclodextrin solutions. J Pharm Sci. 1999 Aug;88(8):759-62.
• [16] Formulation and biopharmaceutical evaluation of transdermal patch containing benztropine. Int J Pharm. 2008 Jun 5;357(1-2):55-60.
• [17] Autonomic cardiovascular control during a novel pharmacologic alternative to ganglionic blockade. Clin Pharmacol Ther. 2008 May;83(5):692-701.
• [18] Negative crosstalk between M1 and M2 muscarinic autoreceptors involves endogenous adenosine activating A1 receptors at the rat motor endplate. Neurosci Lett. 2009 Aug 14;459(3):127-31.
• [19] Capillary gas chromatography of trihexyphenidyl, procyclidine and cycrimine in biological fluids. J Chromatogr. 1989 Sep 29;494:135-42.
• [20] Methylacridinium and its cholinergic properties. Neurotox Res. 2009 Nov;16(4):372-7.
• [21] Cholinergic regulation of the corpora allata in adult male loreyi leafworm Mythimna loreyi. Arch Insect Biochem Physiol. 2002 Apr;49(4):215-24.
• [22] Clinical pipeline report, company report or official report of FemmePharma.
• [23] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [24] Beneficial effect of muscarinic-2 antagonist on dilated cardiomyopathy induced by autoimmune mechanism against muscarinic-2 receptor. J Cardiovasc Pharmacol. 2001 Oct;38 Suppl 1:S43-9.
• [25] Improving the oral efficacy of CNS drug candidates: discovery of highly orally efficacious piperidinyl piperidine M2 muscarinic receptor antagonists. J Med Chem. 2002 Dec 5;45(25):5415-8.
• [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.
• [27] Signal transduction underlying carbachol-induced contraction of human urinary bladder. J Pharmacol Exp Ther. 2004 Jun;309(3):1148-53.
• [28] DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.
• [29] Role of parasympathetic nerves and muscarinic receptors in allergy and asthma.Chem Immunol Allergy.2012;98:48-69.
• [30] 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.
• [31] Muscarinic M3-receptors mediate cholinergic synergism of mitogenesis in airway smooth muscle. Am J Respir Cell Mol Biol. 2003 Feb;28(2):257-62.
• [32] 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.
• [33] 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.
• [34] 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.
• [35] Muscarinic cholinergic and histamine H1 receptor binding of phenothiazine drug metabolites. Life Sci. 1988;43(5):405-12.
• [36] 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.
• [37] Medicinal plants in therapy. Bull World Health Organ. 1985;63(6):965-81.
• [38] Additive protective effects of donepezil and nicotine against salsolinol-induced cytotoxicity in SH-SY5Y cells. Neurotox Res. 2009 Oct;16(3):194-204.
• [39] 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.
• [40] 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).
• [41] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [42] Comparison of pharmacological effects of L- and DL-n-butyl-scopolamine in rat uterus. Yao Xue Xue Bao. 1994;29(1):24-7.
• [43] Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34.