IMIDAFENACIN

Possibly Marketed Outside US

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

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

Molecular Formula	C20H21N3O
Molecular Weight	319.4002
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description

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	Inhibitor 8,504	6.8 nM [IC50]
Muscarinic acetylcholine receptor M1 168	Antagonist 2,849	7.55 nM [Ki]
Muscarinic acetylcholine receptor M3 160	Antagonist 2,849	1.42 nM [Ki]
acetylcholine secretion 4	Inhibitor 8,504	0.747 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Overactive bladder 39	Primary		Approved 8,583	Uritos

C_max

Value	Dose	Analyte	Population
3.86 ng × eq/mL	0.25 mg single, oral	IMIDAFENACIN plasma	Homo sapiens
416 pg/mL	0.1 mg single, oral	IMIDAFENACIN plasma	Homo sapiens
476 pg/mL	0.028 mg single, intravenous	IMIDAFENACIN plasma	Homo sapiens
1240 pg/mL	0.25 mg single, oral	IMIDAFENACIN plasma	Homo sapiens
1240 pg/mL	0.25 mg 2 times / day multiple, oral	IMIDAFENACIN plasma	Homo sapiens
109 pg/mL	0.025 mg single, oral	IMIDAFENACIN plasma	Homo sapiens
180 pg/mL	0.05 mg single, oral	IMIDAFENACIN plasma	Homo sapiens
382 pg/mL	0.1 mg single, oral	IMIDAFENACIN plasma	Homo sapiens
1010 pg/mL	0.25 mg single, oral	IMIDAFENACIN plasma	Homo sapiens
1940 pg/mL	0.5 mg single, oral	IMIDAFENACIN plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
83.06 ng × eq × h/mL	0.25 mg single, oral	IMIDAFENACIN plasma	Homo sapiens
2060 pg × h/mL	0.1 mg single, oral	IMIDAFENACIN plasma	Homo sapiens
993 pg × h/mL	0.028 mg single, intravenous	IMIDAFENACIN plasma	Homo sapiens
5580 pg × h/mL	0.25 mg single, oral	IMIDAFENACIN plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
72.11 h	0.25 mg single, oral	IMIDAFENACIN plasma	Homo sapiens
3 h	0.1 mg single, oral	IMIDAFENACIN plasma	Homo sapiens
3.2 h	0.028 mg single, intravenous	IMIDAFENACIN plasma	Homo sapiens
2.8 h	0.25 mg single, oral	IMIDAFENACIN plasma	Homo sapiens
2.7 h	0.25 mg 2 times / day multiple, oral	IMIDAFENACIN plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
0.25 mg 2 times / day multiple, oral Highest studied dose	healthy, ADULT	Other AEs: Dry mouth...
0.25 mg 2 times / day multiple, oral Highest studied dose	unhealthy, ADULT	Disc. AE: Dry mouth...
0.5 mg single, oral Highest studied dose	healthy, ADULT	Other AEs: Tachyarrhythmia, Dry mouth...

Showing 1 to 3 of 3 entries

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AEs

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AE	Significance	Dose	Population
Dry mouth		0.25 mg 2 times / day multiple, oral Highest studied dose	healthy, ADULT
Dry mouth	8.9% Disc. AE	0.25 mg 2 times / day multiple, oral Highest studied dose	unhealthy, ADULT
Dry mouth		0.5 mg single, oral Highest studied dose	healthy, ADULT
Leucocyturia		0.5 mg single, oral Highest studied dose	healthy, ADULT
Tachyarrhythmia		0.5 mg single, oral Highest studied dose	healthy, ADULT

Showing 1 to 5 of 5 entries

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PubMed

Show entries

Title	Date	PubMed
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

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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.