SOLIFENACIN SUCCINATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H26N2O2.C4H6O4
Molecular Weight	480.5528
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)CCC(O)=O.O=C(O[C@H]1CN2CCC1CC2)N3CCC4=C(C=CC=C4)[C@@H]3C5=CC=CC=C5

InChI

InChIKey=RXZMMZZRUPYENV-VROPFNGYSA-N

InChI=1S/C23H26N2O2.C4H6O4/c26-23(27-21-16-24-13-10-18(21)11-14-24)25-15-12-17-6-4-5-9-20(17)22(25)19-7-2-1-3-8-19;5-3(6)1-2-4(7)8/h1-9,18,21-22H,10-16H2;1-2H2,(H,5,6)(H,7,8)/t21-,22-;/m0./s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021518s016lbl.pdf
Curator's Comment: description was created based on several sources, including: http://www.rxlist.com/vesicare-drug.htm https://www.drugs.com/mtm/solifenacin.html http://www.wikidoc.org/index.php/Solifenacin

Solifenacin is a competitive muscarinic acetylcholine receptor antagonist. The binding of acetylcholine to these receptors, particularly the M3 receptor subtype, plays a critical role in the contraction of smooth muscle. By preventing the binding of acetylcholine to these receptors, solifenacin reduces smooth muscle tone in the bladder, allowing the bladder to retain larger volumes of urine. It is FDA approved for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. Common adverse reactions include constipation, Xerostomia. Inhibitors of CYP3A4 may increase the concentration of Solifenacin. Vice versa, CYP3A4 Inducers decrease concentration.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Muscarinic acetylcholine receptor M3 160 Target ID: CHEMBL245 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021518s016lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/15190387 \| https://www.ncbi.nlm.nih.gov/pubmed/16465186 \| https://www.ncbi.nlm.nih.gov/pubmed/19446545 \| https://www.ncbi.nlm.nih.gov/pubmed/19029429 \| http://www.drugbank.ca/drugs/DB01591	Antagonist 2849	10.0 nM [Ki]
Muscarinic acetylcholine receptor M2 121 Target ID: CHEMBL211 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021518s016lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/16465186 \| https://www.ncbi.nlm.nih.gov/pubmed/19446545 \| https://www.ncbi.nlm.nih.gov/pubmed/19029429 \| http://www.drugbank.ca/drugs/DB01591	Antagonist 2849	125.0 nM [Ki]
Muscarinic acetylcholine receptor M1 168 Target ID: CHEMBL216 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021518s016lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/16465186 \| https://www.ncbi.nlm.nih.gov/pubmed/19029429 \| http://www.drugbank.ca/drugs/DB01591	Antagonist 2849	25.0 nM [Ki]
Muscarinic acetylcholine receptor M4 87 Target ID: CHEMBL1821 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021518s016lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/19029429 \| http://www.drugbank.ca/drugs/DB01591	Antagonist 2849	7.73 null [pKi]
Muscarinic acetylcholine receptor M5 63 Target ID: CHEMBL2035 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021518s016lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/19029429 \| http://www.drugbank.ca/drugs/DB01591	Antagonist 2849	7.46 null [pKi]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency 4 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021518s016lbl.pdf	Primary		Approved 8583	VESICARE Approved Use VESIcare is a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. VESIcare is a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency (1) Launch Date 2004

C_max

Value	Dose	Co-administered	Analyte	Population
14.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15206986	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		SOLIFENACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
820 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15206986	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		SOLIFENACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
50.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15206986	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		SOLIFENACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
2% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021518s012lbl.pdf			SOLIFENACIN plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
100 mg single, oral Highest studied dose Dose: 100 mg Route: oral Route: single Dose: 100 mg Sources: https://pubmed.ncbi.nlm.nih.gov/15317830	healthy, 19-40 Health Status: healthy Age Group: 19-40 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/15317830	Sources: https://pubmed.ncbi.nlm.nih.gov/15317830
30 mg 1 times / day multiple, oral Highest studied dose Dose: 30 mg, 1 times / day Route: oral Route: multiple Dose: 30 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15317830	healthy, 20-35 Health Status: healthy Age Group: 20-35 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/15317830	Sources: https://pubmed.ncbi.nlm.nih.gov/15317830
10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021518s012lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021518s012lbl.pdf	Disc. AE: Angioedema, Anaphylactic reaction... AEs leading to discontinuation/dose reduction: Angioedema Anaphylactic reaction (rare) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021518s012lbl.pdf
10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021518s012lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021518s012lbl.pdf	Disc. AE: Dry mouth... AEs leading to discontinuation/dose reduction: Dry mouth (1.5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021518s012lbl.pdf

AEs

AE	Significance	Dose	Population
Angioedema	Disc. AE	10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021518s012lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021518s012lbl.pdf
Anaphylactic reaction	rare Disc. AE	10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021518s012lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021518s012lbl.pdf
Dry mouth	1.5% Disc. AE	10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021518s012lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021518s012lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252	inhibitor 2438	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A 70 CYP2C19 2057	CYP2C19 1119 CYP3A5 446 CYP2C8 810 CYP1A1 389 P-gp 2052

Drug as perpetrator

Target	Modality	Activity
CYP1A 122	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-518_VESIcare_biopharmr.pdf#page=51 Page: 51.0	not significant
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-518_VESIcare_biopharmr.pdf#page=51 Page: 51.0	not significant
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-518_VESIcare_biopharmr.pdf#page=51 Page: 51.0	not significant
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-518_VESIcare_biopharmr.pdf#page=51 Page: 51.0	not significant
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-518_VESIcare_biopharmr.pdf#page=51 Page: 51.0	yes [Inhibition 1.04 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-518_VESIcare_biopharmr.pdf#page=22 Page: 22,52	major	yes (co-administration study) Comment: Label: coadministration with ketoconazole increased the mean Cmax and AUC of solifenacin by 1.5 and 2.7 fold, respectively; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-518_VESIcare_biopharmr.pdf#page=22 Page: 22,52
CYP1A1 389	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-518_VESIcare_biopharmr.pdf#page=27 Page: 27.0	minor
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-518_VESIcare_biopharmr.pdf#page=22 Page: 22,27	minor
CYP2C8 810	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-518_VESIcare_biopharmr.pdf#page=27 Page: 27.0	minor
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-518_VESIcare_biopharmr.pdf#page=27 Page: 27.0	minor
CYP3A5 446	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-518_VESIcare_biopharmr.pdf#page=27 Page: 27.0	minor
P-gp 2052	substrate 4014 Sources: https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2125.2011.03961.x	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-518_VESIcare_pharmr.pdf#page=35 Page: 35.0

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY543715	https://www.001chemical.com/chem/242478-37-1
AA Blocks	AA019FPZ	https://www.aablocks.com/goods/Goods/detail?id=AA019FPZ
Aaron Chemicals	AR019GHR	http://www.aaronchem.com/242478-37-1
Acadechem	ACDX-012562	http://acadechemical.com/product/87283
Achemo Scientific Limited	AC-63428	http://www.achemo.com/search/?Keyword= 242478-37-1
Achemtek	0102-022129	http://www.achemtek.com/242478-37-1
Acorn PharmaTech	ACN-037989	http://www.acornpharmatech.com/
Adooq BioScience	A16947	https://www.adooq.com/solifenacin.html
AK Scientific, Inc. (AKSCI)	X4689	http://www.aksci.com/item_detail.php?cat=X4689
Alfa Chemistry	242478-37-1	https://www.alfa-chemistry.com/cas_242478-37-1.htm
Alfa Chemistry	ACM180272144	https://www.alfa-chemistry.com/solifenacin-cas-180272-14-4-item-285040.htm
Alichem	189007421	http://www.alichem.com/en/products/180272-14-4.html
Ambinter	Amb20241303	http://www.ambinter.com/reference/20241303
Aurora Fine Chemicals LLC	K16.645.638	http://online.aurorafinechemicals.com/info?ID=K16.645.638
AvaChem Scientific	2557B	http://www.avachem.com/productSearch.asp?2557B
BLD Pharm	BD151698	http://www.bldpharm.com/products/242478-37-1.html
BLD Pharm	BD764111	http://www.bldpharm.com/products/180272-14-4.html
Capot Chemical	23264	http://www.capotchem.com/en/23264.htm
Capot Chemical	PubChem23264	http://www.capotchem.com/en/23264.htm
Chem Scene	CS-8096	http://www.chemscene.com/242478-37-1.html
Chemenu	CM126714	http://www.chemenu.com/products/CM126714
ChemMol	49419563	http://www.chemmol.com/chemmol/49419563.html
Chemspace	CSSB00138412639	https://chem-space.com/CSSB00138412639
Chemspace	CSSS00020667699	https://chem-space.com/CSSS00020667699
Chemspace	CSSS00102523311	https://chem-space.com/CSSS00102523311
Chemspace	CSSS00116206880	https://chem-space.com/CSSS00116206880
CSNpharm	CSN21835	https://www.csnpharm.com/products/solifenacin.html
DC Chemicals	DC9214	http://www.dcchemicals.com/product_show-Solifenacin.html
Debye Scientific	DB-001095	http://www.debyesci.com/DB-001095.html
eNovation Chemicals	D591419	https://www.enovationchem.com/ProductDetails.asp?ProductID=D591419
eNovation Chemicals	D775303	https://www.enovationchem.com/ProductDetails.asp?ProductID=D775303
eNovation Chemicals	D962251	https://www.enovationchem.com/ProductDetails.asp?ProductID=D962251
Excenen	EX-A4180	https://www.excenen.com/searchresultlist.php?id=EX-A4180
Finetech	FT-0698075	http://www.finetechnology-ind.com/prod/detail/pub/242478-37-1.html
Finetech	FT-0778252	https://www.finetechnology-ind.com/prod/detail/pub/180272-14-4.html
Hairui	HR112258	http://www.hairuichem.com/en/product/242478-37-1.html
iChemical	EBD2197604	http://www.ichemical.com/products/242478-37-1.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs
Lab Network	LN01345685	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01345685
MedChem Express	HY-A0034	https://www.medchemexpress.com/Solifenacin.html
Molcore	MC543715	https://www.molcore.com/product/242478-37-1
MolPort	MolPort-023-220-809	https://www.molport.com/shop/molecule-link/MolPort-023-220-809
MolPort	MolPort-046-871-055	https://www.molport.com/shop/molecule-link/MolPort-046-871-055
MuseChem	I012990	https://www.musechem.com/product/I012990.html
OChem	25997	http://www.ocheminc.com/index.php?act=psearch&pid=478S382
Smolecule	S006668	http://www.smolecule.com/products/s006668
Smolecule	S598639	https://www.smolecule.com/products/s598639
Smolecule	S635527	https://www.smolecule.com/products/s635527
Specs	AR-270/43507775	http://www.specs.net/enter.php?specsid=AR-270/43507775
Synblock Inc	SB17427	http://www.synblock.com/product/242478-37-1.html
THE BioTek	bt-255435	https://www.thebiotek.com/product/inhibitors/bt-255435
THE BioTek	bt-339594	https://www.thebiotek.com/product/others/bt-339594
Vitas-M Laboratory	STL484275	http://www.request.vitasmlab.com/index.php?option=com_search_stk&Itemid=22&stk=STL484275&?utm_source=pubchem&utm_medium=p_search_link&utm_campaign=pubchem_search&utm_content=pubchem_slink
Yuhao Chemical	YH48847	http://www.chemyuhao.com/242478-37-1.html

PubMed

Title	Date	PubMed
Gateways to clinical trials.	2003 Nov	14685303
Solifenacin demonstrates high absolute bioavailability in healthy men.	2004	15293866
Drug forecast--solifenacin: an investigational anticholinergic for overactive bladder.	2004 May	16553482
Gateways to clinical trials.	2004 May	15319808
[In overactive bladder, above all urgency is stressful. The patients know the site of each toilet].	2004 May 27	15373116
The emerging role of solifenacin in the treatment of overactive bladder.	2004 Oct	15461562
Pharmacokinetics and safety of solifenacin succinate in healthy young men.	2004 Sep	15317830
Solifenacin in overactive bladder syndrome: a viewpoint by Scott Serels.	2005	16363888
[Neurological aspect of the hyperactive urinary bladder syndrome].	2005	16117151
Improving the tolerability of anticholinergic agents in the treatment of overactive bladder.	2005	15963006
Solifenacin and darifenacin for overactive bladder.	2005 Aug	16055596
Recent developments in the management of overactive bladder: focus on the efficacy and tolerability of once daily solifenacin succinate 5 mg.	2005 Jan	15881477
New molecular entity: Vesicare, Yamanouchi/GlaxoSmithKline solifenacin.	2005 Jan	15700943
Improved quality of life in patients with overactive bladder symptoms treated with solifenacin.	2005 Jan	15638900
Darifenacin in the treatment of overactive bladder.	2005 Jul	15963212
New treatment options for overactive bladder.	2005 Jun	16050656
The Q-T interval and antimuscarinic drugs.	2005 Nov	16238912
Solifenacin versus tolterodine--a head-to-head study: finally! But not final?	2005 Nov	16238911
Solifenacin in the management of the overactive bladder syndrome.	2005 Oct	16178992
Synthesis and antimuscarinic properties of quinuclidin-3-yl 1,2,3,4-tetrahydroisoquinoline-2-carboxylate derivatives as novel muscarinic receptor antagonists.	2005 Oct 20	16220976
Role of muscarinic receptor antagonists in urgency and nocturia.	2005 Sep	16083453
Solifenacin is effective for the treatment of OAB dry patients: a pooled analysis.	2005 Sep	16005564
A comparison of the efficacy and tolerability of solifenacin succinate and extended release tolterodine at treating overactive bladder syndrome: results of the STAR trial.	2005 Sep	15990220
Gateways to clinical trials.	2006 Apr	16810345
New developments in the treatment of urinary incontinence.	2006 Dec	17268395
Solifenacin succinate (VESIcare): overactive bladder therapy.	2006 Dec	17253085
Newer agents for the management of overactive bladder.	2006 Dec 15	17186712
Comparative evaluation of exocrine muscarinic receptor binding characteristics and inhibition of salivation of solifenacin in mice.	2006 Jul	16819176
Management of overactive bladder and urge urinary incontinence in the elderly patient.	2006 Mar	16483866
Pharmacologic management of overactive bladder: practical options for the primary care physician.	2006 Mar	16483865
Using anticholinergics to treat overactive bladder: the issue of treatment tolerability.	2006 Mar	16483863
Gateways to clinical trials.	2006 May	16801985
Pharmacokinetics, safety, and tolerability of solifenacin in patients with renal insufficiency.	2007 Jan	17251687
Solifenacin for overactive bladder with incontinence: symptom bother and health-related quality of life outcomes.	2007 Mar	17341526
An unusual cause of postoperative detrusor overactivity.	2007 Oct	17333438

Patents

Sample Use Guides

In Vivo Use Guide

5 mg tablet taken once daily, and if well tolerated may be increased to 10 mg once daily.

Route of Administration: Oral

In Vitro Use Guide

The inhibitory effect of solifenacin (dose range: 10^-10 - 10^-6 M) for bladder smooth muscle cells (pK(i)=8.12) was 3.6-fold more potent than that for salivary gland cells (pK(i)=7.57).

Name

Type

Language

SOLIFENACIN SUCCINATE

Official Name

English

VESICARE

Preferred Name

English

YM67905

Code

English

SOLIFENACIN SUCCINATE [USAN]

Common Name

English

YM905

Code

English

YM-67905

Code

English

SOLIFENACIN SUCCINATE [USP-RS]

Common Name

English

YM-905

Code

English

SOLIFENACIN SUCCINATE [EP MONOGRAPH]

Common Name

English

SOLIFENACIN SUCCINATE [VANDF]

Common Name

English

VESICARE LS

Brand Name

English

Solifenacin succinate [WHO-DD]

Common Name

English

SOLIFENACIN SUCCINATE [ORANGE BOOK]

Common Name

English

SOLIFENACIN SUCCINATE [MI]

Common Name

English

SOLIFENACIN SUCCINATE [JAN]

Common Name

English

SOLIFENACIN SUCCINATE [MART.]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29704