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

General Information of Drug (ID: DMG592Q)

• Drug Name: Solifenacin Drug Info
• Synonyms: Vesicare; Vesikur; Solifenacin succinate; Solifenacin succinate [USAN]; YM 905; Solifenacin (INN); Solifenacin [INN:BAN]; Vesicare (TN); YM-53705; YM-67905; YM-905; Quinuclidin-3'-yl-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylatemonosuccinate; [(3R)-1-azabicyclo[2.2.2]octan-3-yl] (1S)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate; Butanedioic acid, compd with (1S)-(3R)-1-azabicyclo(2.2.2)oct-3-yl 3,4-dihydro-1-phenyl-2(1H)-isoquinolinecarboxylate (1:1); Butanedioic acid, cmpd. with (1S)-(3R)-1-azabicyclo(2.2.2)oct-3-yl 3,4-dihydro-1-phenyl-2(1H)-isoquinolinecarboxylate (1:1); 1-azabicyclo[2.2.2]oct-8-yl (1S)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate; 1-azabicyclo[2.2.2]octan-3-yl (1S)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate; 2(1H)-Isoquinolinecarboxylic acid, 3,4-dihydro-1-phenyl-, (3R)-1-azabicyclo(2.2.2)oct-3-yl ester, (1S)-, butanedioate (1:1)

Indication

Disease Entry	ICD 11	Status	REF
Overactive bladder	GC50.0	Approved	[1]
Priapism		Investigative	[2]

• Therapeutic Class: Antispasmodics
• Cross-matching ID:
  PubChem CID: 154059
  ChEBI ID: CHEBI:135530
  CAS Number: CAS 242478-37-1
  TTD Drug ID: DMG592Q
  INTEDE Drug ID: DR1497

Molecule-Related Drug Atlas

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	[5]
ACECLIDINE	DMOLNCZ	Glaucoma/ocular hypertension	9C61	Approved	[6]
Tiotropium	DMFDC0Q	Chronic obstructive pulmonary disease	CA22	Approved	[7]
Ipratropium	DMFQ320	Obstructive lung disease	CA22.Z	Approved	[8]
Darifenacin	DMWXLYZ	Overactive bladder	GC50.0	Approved	[9]
Methacholine Chloride	DMGS4QH	Asthma	CA23	Approved	[10]
SMT-D002	DM1I93C	Seborrhea	ED91.2	Approved	[11]
Methylscopolamine	DM5VWOB	Peptic ulcer	DA61	Approved	[12]
Cevimeline	DMWSMND	Sjogren syndrome	4A43.20	Approved	[13]
Methscopolamine Bromide	DMHP8FI	Nausea and vomiting	MD90	Approved	[14]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[15]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[16]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[17]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[18]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[19]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[20]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[21]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[22]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[16]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[23]

Drug(s) Metabolized By Cytochrome P450 2D6 (CYP2D6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[24]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[25]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[26]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[19]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[23]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[27]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[28]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[29]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[30]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[31]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Muscarinic acetylcholine receptor M3 (CHRM3)	TTQ13Z5	ACM3_HUMAN	Antagonist	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[4]
Cytochrome P450 2D6 (CYP2D6) Main DME	DECB0K3	CP2D6_HUMAN	Substrate	[4]

References

• [1] 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: 7483).
• [2] Solifenacin FDA Label
• [3] 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.
• [4] Clinical pharmacokinetics and pharmacodynamics of solifenacin. Clin Pharmacokinet. 2009;48(5):281-302.
• [5] Signal transduction underlying carbachol-induced contraction of human urinary bladder. J Pharmacol Exp Ther. 2004 Jun;309(3):1148-53.
• [6] 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.
• [7] DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.
• [8] Role of parasympathetic nerves and muscarinic receptors in allergy and asthma.Chem Immunol Allergy.2012;98:48-69.
• [9] 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.
• [10] Muscarinic M3-receptors mediate cholinergic synergism of mitogenesis in airway smooth muscle. Am J Respir Cell Mol Biol. 2003 Feb;28(2):257-62.
• [11] Demonstration of bladder selective muscarinic receptor binding by intravesical oxybutynin to treat overactive bladder. J Urol. 2004 Nov;172(5 Pt 1):2059-64.
• [12] 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.
• [13] 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.
• [14] Agonist-regulated alteration of the affinity of pancreatic muscarinic cholinergic receptors. J Biol Chem. 1993 Oct 25;268(30):22436-43.
• [15] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [16] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [17] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [18] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [19] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [20] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [21] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [22] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [23] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [24] Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
• [25] Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
• [26] CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
• [27] Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
• [28] Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
• [29] Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
• [30] Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
• [31] Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.