Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C23H26N2O2 |
Molecular Weight | 362.4656 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
c1ccc(cc1)[C@@]2([H])c3ccccc3CCN2C(=O)O[C@@]4([H])CN5CCC4CC5
InChI
InChIKey=FBOUYBDGKBSUES-VXKWHMMOSA-N
InChI=1S/C23H26N2O2/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/h1-9,18,21-22H,10-16H2/t21-,22-/m0/s1
Molecular Formula | C23H26N2O2 |
Molecular Weight | 362.4656 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionCurator'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
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23094215 http://www.ics.org/Abstracts/Publish/46/000185.pdf
Curator's Comment:: Known to be CNS penetrant in rat. Human data not available
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL245 |
10.0 nM [Ki] | ||
125.0 nM [Ki] | |||
25.0 nM [Ki] | |||
7.73 null [pKi] | |||
7.46 null [pKi] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | VESICARE Approved UseVESIcare 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 Date1.10082235E12 |
Cmax
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 |
T1/2
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 |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2% |
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: Page: p.1028 |
healthy, 19-40 n = 6 Health Status: healthy Age Group: 19-40 Sex: M Population Size: 6 Sources: Page: p.1028 |
|
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: Page: p.1029 |
healthy, 20-35 n = 8 Health Status: healthy Age Group: 20-35 Sex: M Population Size: 8 Sources: Page: p.1029 |
|
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: Page: p.4 |
unhealthy n = 1233 Health Status: unhealthy Condition: Overactive bladder Population Size: 1233 Sources: Page: p.4 |
Disc. AE: Dry mouth... AEs leading to discontinuation/dose reduction: Dry mouth (1.5%) Sources: Page: p.4 |
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: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Overactive bladder Sources: Page: p.1 |
Disc. AE: Angioedema, Anaphylactic reaction... AEs leading to discontinuation/dose reduction: Angioedema Sources: Page: p.1Anaphylactic reaction (rare) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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: Page: p.4 |
unhealthy n = 1233 Health Status: unhealthy Condition: Overactive bladder Population Size: 1233 Sources: Page: p.4 |
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: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Overactive bladder Sources: Page: p.1 |
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: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Overactive bladder Sources: Page: p.1 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-518_VESIcare_biopharmr.pdf#page=51 Page: 51.0 |
not significant | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-518_VESIcare_biopharmr.pdf#page=51 Page: 51.0 |
not significant | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-518_VESIcare_biopharmr.pdf#page=51 Page: 51.0 |
not significant | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-518_VESIcare_biopharmr.pdf#page=51 Page: 51.0 |
not significant | |||
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
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-518_VESIcare_pharmr.pdf#page=35 Page: 35.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Effects of YM905, a novel muscarinic M3-receptor antagonist, on experimental models of bowel dysfunction in vivo. | 2001 Jul |
|
M(3) receptor antagonism by the novel antimuscarinic agent solifenacin in the urinary bladder and salivary gland. | 2002 Aug |
|
Gateways to clinical trials. | 2003 Jul-Aug |
|
Gateways to clinical trials. | 2003 Jun |
|
Gateways to clinical trials. | 2003 Nov |
|
Solifenacin: treatment of overactive bladder. | 2004 Apr |
|
Randomized, double-blind placebo- and tolterodine-controlled trial of the once-daily antimuscarinic agent solifenacin in patients with symptomatic overactive bladder. | 2004 Feb |
|
Solifenacin appears effective and well tolerated in patients with symptomatic idiopathic detrusor overactivity in a placebo- and tolterodine-controlled phase 2 dose-finding study. | 2004 Jan |
|
Comparison of in vitro selectivity profiles of solifenacin succinate (YM905) and current antimuscarinic drugs in bladder and salivary glands: a Ca2+ mobilization study in monkey cells. | 2004 Jan 2 |
|
Food does not affect the pharmacokinetics of solifenacin, a new muscarinic receptor antagonist: results of a randomized crossover trial. | 2004 Jul |
|
Role of antimuscarinics in the treatment of nonneurogenic daytime urinary incontinence in children. | 2004 Mar |
|
Gateways to clinical trials. | 2004 May |
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In vitro and in vivo tissue selectivity profile of solifenacin succinate (YM905) for urinary bladder over salivary gland in rats. | 2004 May 25 |
|
[In overactive bladder, above all urgency is stressful. The patients know the site of each toilet]. | 2004 May 27 |
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Gateways to clinical trials. | 2004 Nov |
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Preview of new drugs for overactive bladder and incontinence: darifenacin, solifenacin, trospium, and duloxetine. | 2004 Oct |
|
The emerging role of solifenacin in the treatment of overactive bladder. | 2004 Oct |
|
[Urinary incontinence: new pharmacologic therapies]. | 2004 Oct-Dec |
|
Pharmacokinetics and safety of solifenacin succinate in healthy young men. | 2004 Sep |
|
[Neurological aspect of the hyperactive urinary bladder syndrome]. | 2005 |
|
Improving the tolerability of anticholinergic agents in the treatment of overactive bladder. | 2005 |
|
New drugs: acamprosate calcium and solifenacin succinate. | 2005 Jan-Feb |
|
New treatment options for overactive bladder. | 2005 Jun |
|
Effect of age on the pharmacokinetics of solifenacin in men and women. | 2005 May |
|
Solifenacin versus tolterodine--a head-to-head study: finally! But not final? | 2005 Nov |
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Open-label study of the safety and pharmacokinetics of solifenacin in subjects with hepatic impairment. | 2006 Dec |
|
Re: Chapple CR, Martinez-Garcia R, Selvaggi L, Toozs-Hobson P, Warnack W, Drogendijk T, Wright DM, Bolodeoku J. A comparison of the efficacy and tolerability of solifenacin succinate and extended release tolterodine at treating overactive bladder syndrome: results of the STAR trial. Eur Urol 2005;48:464-70. | 2006 Jan |
|
Pharmacokinetic effect of ketoconazole on solifenacin in healthy volunteers. | 2006 Jul |
|
[Comment on the STAR study: Comparison of the efficacy and tolerance of solifenacin and tolterodine retard in the treatment of overactive bladder]. | 2006 Jul |
|
[Oral anticholinergics in overactive bladder]. | 2006 Jul |
|
Gateways to clinical trials. | 2006 Jul-Aug |
|
The emergence of new drugs for overactive bladder. | 2006 Mar |
|
Using anticholinergics to treat overactive bladder: the issue of treatment tolerability. | 2006 Mar |
|
Gateways to clinical trials. | 2006 May |
|
Treatment of the overactive bladder syndrome with muscarinic receptor antagonists: a matter of metabolites? | 2006 Nov |
|
Efficacy and tolerability of solifenacin in elderly subjects with overactive bladder syndrome: A pooled analysis. | 2006 Sep |
|
Pharmacokinetics, safety, and tolerability of solifenacin in patients with renal insufficiency. | 2007 Jan |
|
Redefining response in overactive bladder syndrome. | 2007 Jan |
|
Solifenacin for overactive bladder with incontinence: symptom bother and health-related quality of life outcomes. | 2007 Mar |
|
Comparison of the efficacy and tolerability of solifenacin succinate with or without previous use of trospium chloride. | 2007 Sep |
Patents
Sample Use Guides
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15178371
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).
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Jun 25 22:09:49 UTC 2021
by
admin
on
Fri Jun 25 22:09:49 UTC 2021
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Record UNII |
A8910SQJ1U
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Record Status |
Validated (UNII)
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Record Version |
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WHO-ATC |
G04CA53
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NDF-RT |
N0000000125
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WHO-ATC |
G04BD08
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NDF-RT |
N0000000125
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WHO-VATC |
QG04CA53
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LIVERTOX |
892
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NDF-RT |
N0000000125
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WHO-VATC |
QG04BD08
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NCI_THESAURUS |
C29704
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NDF-RT |
N0000175700
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322167
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C441209
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Solifenacin
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M10108
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8155
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DB01591
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SUB21589
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242478-37-1
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242478-37-1
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7483
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CHEMBL1734
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C75284
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A8910SQJ1U
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154059
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SOLIFENACIN
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477364
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ALTERNATIVE |
Related Record | Type | Details | ||
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TARGET -> INHIBITOR |
Appears to be more bladder-selective for the M3 receptor relative to salivary glands.eptor
Ki
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METABOLIC ENZYME -> SUBSTRATE |
MINOR
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TARGET->WEAK INHIBITOR |
Ki
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BINDER->LIGAND |
in vivo
BINDING
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EXCRETED UNCHANGED |
URINE
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METABOLIC ENZYME -> SUBSTRATE |
MAJOR
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SALT/SOLVATE -> PARENT | |||
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SALT/SOLVATE -> PARENT | |||
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TARGET -> INHIBITOR |
Ki
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Related Record | Type | Details | ||
---|---|---|---|---|
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METABOLITE INACTIVE -> PARENT |
major in urine
MAJOR
PLASMA; URINE
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METABOLITE ACTIVE -> PARENT |
major in urine
MAJOR
PLASMA; URINE
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METABOLITE INACTIVE -> PARENT |
MINOR
PLASMA
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METABOLITE ACTIVE -> PARENT |
occurs at low concentrations and unlikely to contribute significantly to clinical activity
MINOR
PLASMA
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METABOLITE ACTIVE -> PARENT |
MAJOR
URINE
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METABOLITE ACTIVE -> PARENT |
FECAL
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Volume of Distribution | PHARMACOKINETIC |
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Tmax | PHARMACOKINETIC |
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ORAL ADMINISTRATION |
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Biological Half-life | PHARMACOKINETIC |
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