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

General Information of Drug (ID: DMLN0Y5)

• Drug Name: Alvameline Drug Info
• Synonyms: Alvameline maleate; LU-25077; LU-25109; LU-31126; LU-32181; Lu-25109M

Indication

Disease Entry	ICD 11	Status	REF
Alzheimer disease	8A20	Terminated	[1]

• Cross-matching ID:
  PubChem CID: 178030
  CAS Number: CAS 120241-31-8
  TTD Drug ID: DMLN0Y5

Molecule-Related Drug Atlas

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	[3]
SMT-D002	DM1I93C	Seborrhea	ED91.2	Approved	[4]
Clidinium	DMUMQZ0	Abdominal stomach pain	DD91.4	Approved	[5]
Trihexyphenidyl	DMB19L8	Dystonia	8A02	Approved	[6]
Oxyphenonium	DMMQHOZ	Visceral spasms	MD81.4	Approved	[7]
Benztropine	DMGZOVN	Parkinson disease	8A00.0	Approved	[8]
Glycopyrrolate	DM2M3ZA	Anaesthesia	9A78.6	Approved	[9]
Pirenzepine	DMP6M1N	Peptic ulcer	DA61	Approved	[10]
Cycrimine	DM8C43Q	Parkinson disease	8A00.0	Approved	[11]

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	[12]
SMT-D002	DM1I93C	Seborrhea	ED91.2	Approved	[4]
Methylscopolamine	DM5VWOB	Peptic ulcer	DA61	Approved	[13]
Gallamine Triethiodide	DMPO0MS	Stabilize muscle contraction	FB3Z	Approved	[14]
FP-1097	DMC1F2T	Urinary incontinence	MF50.2	Phase 2	[15]
PSD-506	DMT0KB1	Overactive bladder	GC50.0	Discontinued in Phase 2	[16]
Otenzepad	DMRXHAC	Heart failure	BD10-BD13	Discontinued in Phase 2	[17]
SCH-211803	DM92E0W	Parkinson disease	8A00.0	Discontinued in Phase 1	[18]
HIMBACINE	DMGAKD8	N. A.	N. A.	Terminated	[19]

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	[20]
ACECLIDINE	DMOLNCZ	Glaucoma/ocular hypertension	9C61	Approved	[2]
Tiotropium	DMFDC0Q	Chronic obstructive pulmonary disease	CA22	Approved	[21]
Ipratropium	DMFQ320	Obstructive lung disease	CA22.Z	Approved	[22]
Darifenacin	DMWXLYZ	Overactive bladder	GC50.0	Approved	[23]
Methacholine Chloride	DMGS4QH	Asthma	CA23	Approved	[24]
SMT-D002	DM1I93C	Seborrhea	ED91.2	Approved	[4]
Solifenacin	DMG592Q	Overactive bladder	GC50.0	Approved	[25]
Methylscopolamine	DM5VWOB	Peptic ulcer	DA61	Approved	[26]
Cevimeline	DMWSMND	Sjogren syndrome	4A43.20	Approved	[27]

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	Modulator	[1]
Muscarinic acetylcholine receptor M2 (CHRM2)	TTYEG6Q	ACM2_HUMAN	Modulator	[1]
Muscarinic acetylcholine receptor M3 (CHRM3)	TTQ13Z5	ACM3_HUMAN	Modulator	[1]

References

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• [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] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] Demonstration of bladder selective muscarinic receptor binding by intravesical oxybutynin to treat overactive bladder. J Urol. 2004 Nov;172(5 Pt 1):2059-64.
• [5] Accidental acute clidinium toxicity. Emerg Med J. 2009 Jun;26(6):460.
• [6] 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.
• [7] Ultraviolet spectroscopic estimation of microenvironments and bitter tastes of oxyphenonium bromide in cyclodextrin solutions. J Pharm Sci. 1999 Aug;88(8):759-62.
• [8] Formulation and biopharmaceutical evaluation of transdermal patch containing benztropine. Int J Pharm. 2008 Jun 5;357(1-2):55-60.
• [9] Autonomic cardiovascular control during a novel pharmacologic alternative to ganglionic blockade. Clin Pharmacol Ther. 2008 May;83(5):692-701.
• [10] 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.
• [11] Capillary gas chromatography of trihexyphenidyl, procyclidine and cycrimine in biological fluids. J Chromatogr. 1989 Sep 29;494:135-42.
• [12] 6beta-Acetoxynortropane: a potent muscarinic agonist with apparent selectivity toward M2-receptors. J Med Chem. 1998 Jun 4;41(12):2047-55.
• [13] Methylacridinium and its cholinergic properties. Neurotox Res. 2009 Nov;16(4):372-7.
• [14] Cholinergic regulation of the corpora allata in adult male loreyi leafworm Mythimna loreyi. Arch Insect Biochem Physiol. 2002 Apr;49(4):215-24.
• [15] Clinical pipeline report, company report or official report of FemmePharma.
• [16] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [17] 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.
• [18] 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.
• [19] Himbacine analogs as muscarinic receptor antagonists--effects of tether and heterocyclic variations. Bioorg Med Chem Lett. 2004 Aug 2;14(15):3967-70.
• [20] Signal transduction underlying carbachol-induced contraction of human urinary bladder. J Pharmacol Exp Ther. 2004 Jun;309(3):1148-53.
• [21] DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.
• [22] Role of parasympathetic nerves and muscarinic receptors in allergy and asthma.Chem Immunol Allergy.2012;98:48-69.
• [23] 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.
• [24] Muscarinic M3-receptors mediate cholinergic synergism of mitogenesis in airway smooth muscle. Am J Respir Cell Mol Biol. 2003 Feb;28(2):257-62.
• [25] 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.
• [26] 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.
• [27] 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.