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
SMILES
OC(=O)CCC(O)=O.O=C(O[C@H]1CN2CCC1CC2)N3CCC4=CC=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
Molecular Formula | C4H6O4 |
Molecular Weight | 118.088 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Molecular Formula | C23H26N2O2 |
Molecular Weight | 362.4647 |
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 |
---|---|---|
Gateways to clinical trials. | 2003 Jul-Aug |
|
Gateways to clinical trials. | 2003 Jun |
|
Solifenacin demonstrates high absolute bioavailability in healthy men. | 2004 |
|
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 |
|
[Overactive bladder. New anticholinergic drug controls urinary urge]. | 2004 Jul 8 |
|
Role of antimuscarinics in the treatment of nonneurogenic daytime urinary incontinence in children. | 2004 Mar |
|
Randomized, double-blind placebo controlled trial of the once daily antimuscarinic agent solifenacin succinate in patients with overactive bladder. | 2004 Nov |
|
Elevating our therapeutic expectations in overactive bladder. | 2004 Oct |
|
[Urinary incontinence: new pharmacologic therapies]. | 2004 Oct-Dec |
|
[Urinary incontinence: anticholinergic treatment]. | 2004 Oct-Dec |
|
Solifenacin in overactive bladder syndrome: a viewpoint by Scott Serels. | 2005 |
|
[Neurological aspect of the hyperactive urinary bladder syndrome]. | 2005 |
|
Effects of solifenacin succinate (YM905) on detrusor overactivity in conscious cerebral infarcted rats. | 2005 Apr 4 |
|
Solifenacin and darifenacin for overactive bladder. | 2005 Aug |
|
[Medical therapy of urinary incontinence]. | 2005 Jan |
|
New drugs: acamprosate calcium and solifenacin succinate. | 2005 Jan-Feb |
|
Long-term open-label solifenacin treatment associated with persistence with therapy in patients with overactive bladder syndrome. | 2005 Mar |
|
Muscarinic receptor binding, plasma concentration and inhibition of salivation after oral administration of a novel antimuscarinic agent, solifenacin succinate in mice. | 2005 May |
|
Solifenacin versus tolterodine--a head-to-head study: finally! But not final? | 2005 Nov |
|
Solifenacin in the management of the overactive bladder syndrome. | 2005 Oct |
|
Solifenacin is effective for the treatment of OAB dry patients: a pooled analysis. | 2005 Sep |
|
Gateways to clinical trials. | 2006 Apr |
|
Multiple doses of the antimuscarinic agent solifenacin do not affect the pharmacodynamics or pharmacokinetics of warfarin or the steady-state pharmacokinetics of digoxin in healthy subjects. | 2006 Aug |
|
New drugs 06, part I. | 2006 Feb |
|
[Oral anticholinergics in overactive bladder]. | 2006 Jul |
|
Gateways to clinical trials. | 2006 Jul-Aug |
|
Efficacy and tolerability of solifenacin in elderly subjects with overactive bladder syndrome: a pooled analysis. | 2006 Mar |
|
Treatment of the overactive bladder syndrome with muscarinic receptor antagonists: a matter of metabolites? | 2006 Nov |
|
Reductions in overactive bladder-related incontinence from pooled analysis of phase III trials evaluating treatment with solifenacin. | 2006 Sep |
|
Pharmacokinetics, safety, and tolerability of solifenacin in patients with renal insufficiency. | 2007 Jan |
|
Pharmacological characterization of a new antimuscarinic agent, solifenacin succinate, in comparison with other antimuscarinic agents. | 2007 Jan |
|
Nocturnal polyuria and nocturia relief in patients treated with solifenacin for overactive bladder symptoms. | 2007 Jul |
|
Solifenacin for overactive bladder with incontinence: symptom bother and health-related quality of life outcomes. | 2007 Mar |
|
An unusual cause of postoperative detrusor overactivity. | 2007 Oct |
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
Wed Jul 05 23:59:16 UTC 2023
by
admin
on
Wed Jul 05 23:59:16 UTC 2023
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Record UNII |
KKA5DLD701
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Record Status |
Validated (UNII)
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Record Version |
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C29704
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PARENT -> SALT/SOLVATE | |||
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PARENT -> SALT/SOLVATE |
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