TROSPIUM

Details

Stereochemistry	ACHIRAL
Molecular Formula	C25H30NO3
Molecular Weight	392.5106
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	1

SHOW SMILES / InChI

Structure Search

SMILES

OC(C(=O)O[C@@H]1C[C@@H]2CC[C@H](C1)[N@@+]23CCCC3)(C4=CC=CC=C4)C5=CC=CC=C5

InChI

InChIKey=OYYDSUSKLWTMMQ-JKHIJQBDSA-N

InChI=1S/C25H30NO3/c27-24(25(28,19-9-3-1-4-10-19)20-11-5-2-6-12-20)29-23-17-21-13-14-22(18-23)26(21)15-7-8-16-26/h1-6,9-12,21-23,28H,7-8,13-18H2/q+1/t21-,22+,23+

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021595s008lbl.pdf
Curator's Comment: Description was created based on several sources, including https://www.drugbank.ca/drugs/DB00209

Trospium is an antispasmodic, antimuscarinic agent indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. Receptor assays showed that trospium has negligible affinity for nicotinic receptors as compared to muscarinic receptors at concentrations obtained from therapeutic doses. Trospium antagonizes the effect of acetylcholine on muscarinic receptors in cholinergically innervated organs. Its parasympatholytic action reduces the tonus of smooth muscle in the bladder. Trospium is marketed under the brand name Sancturain the US, Tropez OD in India,Trosec in Canada, Regurin and Flotros in the United Kingdom and Spasmex in Germany, Russia, Turkey, Argentina, Chile and Israel.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Muscarinic acetylcholine receptor 160 Target ID: CHEMBL2094109 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021595s008lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/15723094 \| http://www.genome.jp/dbget-bin/www_bget?D01103 \| https://www.ncbi.nlm.nih.gov/pubmed/19029429	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Overactive bladder 38 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021595s008lbl.pdf	Primary		Approved 8429	SANCTURA Approved Use Trospium chloride tablets are a muscarinic antagonist indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency. Trospium chloride tablets are a muscarinic antagonist indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency. (1) Launch Date 2004

C_max

Value	Dose	Co-administered	Analyte	Population
3.5 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021595s009lbl.pdf	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		TROSPIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
36.4 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021595s009lbl.pdf	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		TROSPIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
18.3 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021595s009lbl.pdf	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		TROSPIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
32.5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021595s009lbl.pdf	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		TROSPIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
360 mg single, oral Highest studied dose Dose: 360 mg Route: oral Route: single Dose: 360 mg Sources: https://pubmed.ncbi.nlm.nih.gov/8494577 https://pubmed.ncbi.nlm.nih.gov/18360555	healthy n = 8 Health Status: healthy Sex: M Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/8494577 https://pubmed.ncbi.nlm.nih.gov/18360555	Sources: https://pubmed.ncbi.nlm.nih.gov/8494577 https://pubmed.ncbi.nlm.nih.gov/18360555
20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021595s009lbl.pdf Page: p.3	unhealthy n = 591 Health Status: unhealthy Condition: Overactive bladder Population Size: 591 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021595s009lbl.pdf Page: p.3	Disc. AE: Dry mouth... AEs leading to discontinuation/dose reduction: Dry mouth (1.9%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021595s009lbl.pdf Page: p.3
20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021595s009lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Overactive bladder Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021595s009lbl.pdf Page: p.1	Disc. AE: Face angioedema, Lip angioedema... AEs leading to discontinuation/dose reduction: Face angioedema Lip angioedema Oedema tongue Angioedema of larynx Somnolence Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021595s009lbl.pdf Page: p.1

AEs

AE	Significance	Dose	Population
Dry mouth	1.9% Disc. AE	20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021595s009lbl.pdf Page: p.3	unhealthy n = 591 Health Status: unhealthy Condition: Overactive bladder Population Size: 591 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021595s009lbl.pdf Page: p.3
Angioedema of larynx	Disc. AE	20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021595s009lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Overactive bladder Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021595s009lbl.pdf Page: p.1
Face angioedema	Disc. AE	20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021595s009lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Overactive bladder Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021595s009lbl.pdf Page: p.1
Lip angioedema	Disc. AE	20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021595s009lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Overactive bladder Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021595s009lbl.pdf Page: p.1
Oedema tongue	Disc. AE	20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021595s009lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Overactive bladder Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021595s009lbl.pdf Page: p.1
Somnolence	Disc. AE	20 mg 2 times / day multiple, oral Recommended Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021595s009lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Overactive bladder Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021595s009lbl.pdf Page: p.1

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2A6 707 CYP2C19 1478 CYP2E1 882	esterase 72	CYP 76

Drug as perpetrator

Target	Modality	Activity
CYP 147	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-595_Sanctura_BioPharmr_P1.pdf Page: 47.0	inconclusive
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022103s000_ClinPharmR.pdf Page: 22.0	no [IC50 11928 uM]
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022103s000_ClinPharmR.pdf Page: 22.0	no [IC50 14857 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022103s000_ClinPharmR.pdf Page: 22.0	no [IC50 1756.3 uM]
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022103s000_ClinPharmR.pdf Page: 22.0	no [IC50 2000 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022103s000_ClinPharmR.pdf Page: 22.0	no [IC50 2600 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022103s000_ClinPharmR.pdf Page: 22.0	no [IC50 27 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022103s000_ClinPharmR.pdf Page: 22.0	no [IC50 8432 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
esterase 72	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022103s000_ClinPharmR.pdf Page: 22.0	likely

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022103s000_PharmR.pdf Page: 5, 13

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:145791	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:145791
ZINC	ZINC000100016084	http://zinc15.docking.org/substances/ZINC000100016084

PubMed

Title	Date	PubMed
Trospium chloride: a quaternary amine with unique pharmacologic properties.	2003 Dec	14622495

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose of SANCTURA (Trospium) is one 20 mg tablet twice daily. SANCTURA should be dosed with water on an empty stomach, at least one hour before a meal. For patients with severe renal impairment (creatinine clearance less than 30 mL/min), the recommended dose is 20 mg once daily at bedtime. In geriatric patients greater than or equal to 75 years of age, dose may be titrated down to 20 mg once daily based upon tolerability.

Route of Administration: Oral

In Vitro Use Guide

After cumulative administration of increasing concentrations of trospium (1, 3, and 5 uM), agonist-induced contractions decreased significantly in bladder strips.

Name

Type

Language

TROSPIUM

Common Name

English

Trospium [WHO-DD]

Common Name

English

TROSPIUM ION

Common Name

English

TROSPIUM [VANDF]

Common Name

English

TROSPIUM CATION

Common Name

English

3.ALPHA.-HYDROXYSPIRO(1.ALPHA.H,5.ALPHA.H-NORTROPANE-8,1'-PYRROLIDINIUM) BENZILATE

Common Name

English

SPIRO(8-AZONIABICYCLO(3.2.1)OCTANE-8,1'-PYRROLIDINIUM), 3-((HYDROXYDIPHENYLACETYL)OXY)-, (1.ALPHA.,3.BETA.,5.ALPHA.)-

Common Name

English

Classification Tree Code System Code

WHO-VATC

QA03DA06