DARIFENACIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C28H30N2O2
Molecular Weight	426.55
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

NC(=O)C([C@@H]1CCN(CCC2=CC3=C(OCC3)C=C2)C1)(C4=CC=CC=C4)C5=CC=CC=C5

InChI

InChIKey=HXGBXQDTNZMWGS-RUZDIDTESA-N

InChI=1S/C28H30N2O2/c29-27(31)28(23-7-3-1-4-8-23,24-9-5-2-6-10-24)25-14-17-30(20-25)16-13-21-11-12-26-22(19-21)15-18-32-26/h1-12,19,25H,13-18,20H2,(H2,29,31)/t25-/m1/s1

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Description

Darifenacin is a selective muscarinic receptor M3 antagonist which was approved by FDA for the treatment of overactive bladder.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Muscarinic acetylcholine receptor M3 160	Antagonist 2,849		0.33 nM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Overactive bladder 39	Palliative		Approved 8,583	ENABLEX

C_max

Value	Dose	Co-administered	Analyte	Population
2.01 ng/mL	7.5 mg 1 times / day steady-state, oral		DARIFENACIN plasma	Homo sapiens
5.76 ng/mL	15 mg 1 times / day steady-state, oral		DARIFENACIN plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
29.24 ng × h/mL	7.5 mg 1 times / day steady-state, oral		DARIFENACIN plasma	Homo sapiens
88.9 ng × h/mL	15 mg 1 times / day steady-state, oral		DARIFENACIN plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
12.43 h	7.5 mg 1 times / day steady-state, oral		DARIFENACIN plasma	Homo sapiens
12.05 h	15 mg 1 times / day steady-state, oral		DARIFENACIN plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
2%	7.5 mg 1 times / day steady-state, oral		DARIFENACIN plasma	Homo sapiens
2%	15 mg 1 times / day steady-state, oral		DARIFENACIN plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
15 mg 1 times / day multiple, oral Recommended	unhealthy, 57.6	Disc. AE: Constipation, Dry mouth...
7.5 mg 1 times / day multiple, oral Recommended	unhealthy, 57.6	Disc. AE: Heart block AV second degree...

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AEs

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AE	Significance	Dose	Population
Nervous system disorder NOS	0.6% Disc. AE	15 mg 1 times / day multiple, oral Recommended	unhealthy, 57.6
Constipation	1% Disc. AE	15 mg 1 times / day multiple, oral Recommended	unhealthy, 57.6
Dry mouth	1% Disc. AE	15 mg 1 times / day multiple, oral Recommended	unhealthy, 57.6
Heart block AV second degree	0.3% Disc. AE	7.5 mg 1 times / day multiple, oral Recommended	unhealthy, 57.6

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,946 inhibitor 2,252	inhibitor 2,438	substrate 1,388 inhibitor 2,507	inhibitor 2,217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2,153	P-gp 2,052 BCRP 697 MRP 9

Drug as perpetrator

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Target	Modality	Activity	Clinical evidence
CYP1A2 2,333	inhibitor 4,027	no
CYP2C9 2,497	inhibitor 4,027	no
CYP2D6 2,546	inhibitor 4,027	yes [IC50 2 uM]	yes (co-administration study)
CYP3A4 2,633	inhibitor 4,027	yes [IC50 5 uM]	weak (co-administration study)

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Drug as victim

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Target	Modality	Activity	Clinical evidence
CYP2D6 1,388	substrate 4,014	major	yes (co-administration study)
CYP3A4 1,946	substrate 4,014	major	yes (co-administration study)
BCRP 697	substrate 4,014	unresponsive
MRP 9	substrate 4,014	unresponsive
P-gp 2,052	substrate 4,014	yes

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Tox targets

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Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2,263	inhibitor 2,237

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
ChEBI	CHEBI:391960	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:391960
ChemicalBook	CB1506695	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1506695
MolPort	MolPort-005-943-011	https://www.molport.com/shop/molecule-link/MolPort-005-943-011
ZINC	ZINC000001996117	http://zinc15.docking.org/substances/ZINC000001996117

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PubMed

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Title	Date	PubMed
Anticholinergic drugs versus placebo for overactive bladder syndrome in adults.	2002	12137711
M(3) receptor antagonism by the novel antimuscarinic agent solifenacin in the urinary bladder and salivary gland.	2002 Aug	12122494
Model of rapid gastrointestinal transit in dogs: effects of muscarinic antagonists and a nitric oxide synthase inhibitor.	2002 Oct	12358682
Demonstration of functional M3-muscarinic receptors in ventricular cardiomyocytes of adult rats.	2003 Jan	12522085
Update on overactive bladder: pharmacologic approaches on the horizon.	2003 Oct	14499063

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Patents

Sample Use Guides

In Vivo Use Guide

The recommended starting dose of darifenacin extended-release tablets (Enablex) is 7.5 mg once daily.

Route of Administration: Oral

In Vitro Use Guide

Bladder smooth muscle and submandibular gland cells isolated from Cynomolgus monkeys were treated with darifenacin and pKi values obtained in Ca2+ mobilization assay were 8,4 and 8,8, respectively.

Show entries

Name

Type

Language

UK-88525

Preferred Name

English

DARIFENACIN

Official Name

English

3-PYRROLIDINEACETAMIDE, 1-(2-(2,3-DIHYDRO-5-BENZOFURANYL)ETHYL)-.ALPHA.,.ALPHA.-DIPHENYL-, (3S)-

Systematic Name

English

darifenacin [INN]

Common Name

English

2-((3S)-1-(2-(2,3-DIHYDROBENZOFURAN-5-YL)ETHYL)PYRROLIDIN-3-YL)-2,2-DIPHENYLACETAMIDE.

Common Name

English

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Classification Tree

Code System

Code

Anticholinergic Agent

NCI_THESAURUS

C29704

Cholinergic Antagonists

NDF-RT

N0000000125

Established Pharmacologic Class

NDF-RT

N0000175700

Agent Affecting Nervous System

NCI_THESAURUS

C29698

Drugs for urinary frequency and incontinence

WHO-VATC

QG04BD10

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Code System

Code

Type

Description

SMS_ID

100000085412

PRIMARY

CHEBI

391960

PRIMARY

USAN

RR-29

PRIMARY

DAILYMED

APG9819VLM

PRIMARY

FDA UNII

APG9819VLM

PRIMARY

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ACTIVE MOIETY


					APG9819VLM

DARIFENACIN

METABOLITE (PARENT)


					XPC5K28NQA

UK-156981 ACID

METABOLITE (PARENT)


					GKS9J5ENH7

UK-148993

METABOLITE (PARENT)


					LJC7B2CBF2

2,3-DIHYDROBENZOFURAN-5-ACETIC ACID

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator