IMIDAFENACIN

Details

Stereochemistry	ACHIRAL
Molecular Formula	C20H21N3O
Molecular Weight	319.4002
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=NC=CN1CCC(C(N)=O)(C2=CC=CC=C2)C3=CC=CC=C3

InChI

InChIKey=SQKXYSGRELMAAU-UHFFFAOYSA-N

InChI=1S/C20H21N3O/c1-16-22-13-15-23(16)14-12-20(19(21)24,17-8-4-2-5-9-17)18-10-6-3-7-11-18/h2-11,13,15H,12,14H2,1H3,(H2,21,24)

HIDE SMILES / InChI

Description
Sources: http://www.ncbi.nlm.nih.gov/pubmed/23641864
Curator's Comment: Description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/25636812

Imidafenacin (KRP-197/ONO-8025) is the latest antimuscarinic (AM) developed for the treatment of overactive bladder syndrome (OAB) and, at the moment, it is marketed only in Japan. It has high affinities for the M3 and M1 muscarinic receptor subtypes, a low affinity for M2 receptors, and a potent inhibitory activity against rhythmic bladder contractions. Imidafenacin has excellent efficacy, tolerability, and safety. It is indicated for patients with nocturia, nocturnal polyuria, and benign prostatic hyperplasia.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
potassium ion transport 2 Target ID: GO:0006813 Sources: http://www.ncbi.nlm.nih.gov/pubmed/17396619	Inhibitor 8297	6.8 nM [IC50]
Muscarinic acetylcholine receptor M1 169 Target ID: CHEMBL216 Sources: http://www.ncbi.nlm.nih.gov/pubmed/17396619	Antagonist 2778	7.55 nM [Ki]
Muscarinic acetylcholine receptor M3 159 Target ID: CHEMBL245 Sources: http://www.ncbi.nlm.nih.gov/pubmed/17396619	Antagonist 2778	1.42 nM [Ki]
acetylcholine secretion 4 Target ID: GO:0061526 Sources: http://www.ncbi.nlm.nih.gov/pubmed/17396619	Inhibitor 8297	0.747 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Overactive bladder 38 Sources: http://www.kyorin-pharm.co.jp/en/news/docs/ut.pdf	Primary		Approved 8429	Uritos Approved Use For the treatment of Overactive bladder Launch Date 2007

PubMed

Title	Date	PubMed
Synthesis and antimuscarinic activity of a series of 4-(1-Imidazolyl)-2,2-diphenylbutyramides: discovery of potent and subtype-selective antimuscarinic agents.	1999 Jun	10428387
Biomimetic oxidation of 2-methylimidazole derivative with a chemical model system for cytochrome P-450.	2002 Aug	12192156
Pharmacological effects of KRP-197 on the human isolated urinary bladder.	2003	14512651
Pharmacological effects of imidafenacin (KRP-197/ONO-8025), a new bladder selective anti-cholinergic agent, in rats. Comparison of effects on urinary bladder capacity and contraction, salivary secretion and performance in the Morris water maze task.	2007	17469649
Effects of imidafenacin (KRP-197/ONO-8025), a new anti-cholinergic agent, on muscarinic acetylcholine receptors. High affinities for M3 and M1 receptor subtypes and selectivity for urinary bladder over salivary gland.	2007	17396619
Drug-drug interactions in the metabolism of imidafenacin: role of the human cytochrome P450 enzymes and UDP-glucuronic acid transferases, and potential of imidafenacin to inhibit human cytochrome P450 enzymes.	2007 Feb	17484517
Synthesis of the metabolites of 4-(2-methyl-1H-imidazol-1-yl)-2,2-diphenylbutanamide (KRP-197/ONO-8025).	2007 Jul	17603197
Development and validation of bioanalytical methods for Imidafenacin (KRP-197/ONO-8025) and its metabolites in human plasma by liquid chromatography-tandem mass spectrometry.	2007 Jun 15	17387045
Absorption, metabolism, and excretion of [14C]imidafenacin, a new compound for treatment of overactive bladder, after oral administration to healthy male subjects.	2007 Sep	17567733
Development and validation of bioanalytical methods for imidafenacin (KRP-197/ONO-8025) and its metabolites in human urine by using liquid chromatography-tandem mass spectrometry.	2007 Sep	17474137
Population pharmacokinetic analysis of a novel muscarinic receptor antagonist, imidafenacin, in healthy volunteers and overactive bladder patients.	2008	19122340
No effect of imidafenacin, a novel antimuscarinic drug, on digoxin pharmacokinetics in healthy subjects.	2008	18445988
Absolute bioavailability of imidafenacin after oral administration to healthy subjects.	2008 Feb	18251758
Validation and application of a 96-well format solid-phase extraction and liquid chromatography-tandem mass spectrometry method for the quantitation of digoxin in human plasma.	2008 Jun 15	18515196
Effect of itraconazole on the pharmacokinetics of imidafenacin in healthy subjects.	2008 Mar	18218784
[Pharmacological and clinical profile of imidafenacin developed as a new therapeutic agent for overactive bladder].	2008 May	18480570
Long-term safety, tolerability, and efficacy of the novel anti-muscarinic agent imidafenacin in Japanese patients with overactive bladder.	2008 Oct	18761536
A randomized, double-blind, placebo-controlled phase II dose-finding study of the novel anti-muscarinic agent imidafenacin in Japanese patients with overactive bladder.	2008 Sep	18637156
Response to "Suspected differential interactions of digoxin with imidafenacin and propantheline; some thoughts for introspection".	2009	19881263
Suspected differential interactions of digoxin with imidafenacin and propantheline; some thoughts for introspection.	2009	19430177
Comparison of the effect of anti-muscarinic agents on bladder activity, urinary ATP level, and autonomic nervous system in rats.	2009 Apr	19420734
A randomized, double-blind, placebo- and propiverine-controlled trial of the novel antimuscarinic agent imidafenacin in Japanese patients with overactive bladder.	2009 May	19389083
The add-on effect of solifenacin for patients with remaining overactive bladder after treatment with tamsulosin for lower urinary tract symptoms suggestive of benign prostatic obstruction.	2010	20981257
Noninvasive evaluation of brain muscarinic receptor occupancy of oxybutynin, darifenacin and imidafenacin in rats by positron emission tomography.	2010 Jul 31	20598326
Application of a novel combination of near-infrared spectroscopy and a humidity-controlled 96-well plate to the characterization of the polymorphism of imidafenacin.	2010 Nov	21039538

Patents

Sample Use Guides

In Vivo Use Guide

Usually, for adults, a single dose of 0.1mg as imidafenacin is orally administered, twice daily, after each meal in the morning and evening. If the desired efficacy is not observed a single dose can be increased up to 0.2mg (0.4mg daily).

Route of Administration: Oral

In Vitro Use Guide

10(–8) to 10(–7) M Imidafenacin (KRP-197) significantly decreased electrical field stimulation-induced acetylcholine release and the contractile responses in a concentration-dependent manner.

Name

Type

Language

IMIDAFENACIN

Official Name

English

URITOS

Brand Name

English

STAYBLA

Brand Name

English

IMIDAFENACIN [JAN]

Common Name

English

KRP-197

Code

English

IMIDAFENACIN [MART.]

Common Name

English

ONO-8025

Code

English

Imidafenacin [WHO-DD]

Common Name

English

imidafenacin [INN]

Common Name

English

IMIDAFENACIN [MI]

Common Name

English

4-(2-METHYL-1H-IMIDAZOL-1-YL)-2,2-DIPHENYLBUTANAMIDE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29704