Explore a selection of our essential drug information below, or:
Identification
- Summary
Imidafenacin is an antispasmodic with anticholinergic effects used to reduce urinary frequency.
- Generic Name
- Imidafenacin
- DrugBank Accession Number
- DB09262
- Background
Imidafenacin is an antispasmodic agent with anticholinergic effects. It antagonizes muscarinic receptors in the bladder to reduce the frequency of urination in the treatment of overactive bladder. It is marketed in Japan under the tradenames Staybla by Ono Pharmaceutical and Uritos by Kyojin Pharmaceutical.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Imidafenacin (DB09262)
- Weight
- Average: 319.408
Monoisotopic: 319.168462308 - Chemical Formula
- C20H21N3O
- Synonyms
- Imidafenacin
- External IDs
- KRP-197
- KRP-1979
- Ono-8025
Pharmacology
- Indication
Used in the treatment of overactive bladder Label.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Urinary bladder, overactive •••••••••••• ••••••• ••••••• ••••••• •••• •••••• Treatment of Urinary bladder, overactive •••••••••••• •••••• Treatment of Urinary frequency •••••••••••• ••••••• ••••••• ••••••• •••• •••••• Treatment of Urinary frequency •••••••••••• •••••• Treatment of Urinary incontinence (ui) •••••••••••• ••••••• ••••••• ••••••• •••• •••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Imidafenacin is an antimuscarinic agent which acts to reduce the frequency of urination in patients with overactive bladder Label.
- Mechanism of action
Imidafenacin binds to and antagonizes muscarinic M1 and M3 receptors with high affinity 3. It also antagonizes muscarinic M2 receptors but with lower affinity. M3 receptors stimulate contraction of the detrusor muscle in the bladder via release of calcium from the sarcoplasmic reticulum 4. M2 receptors are also present in the detrusor muscle but serve to inhibit adenylate cyclase which reduces the relaxation mediated by β adrenergic receptors. Finally, M1 receptors are present on the parasympathetic neurons which release acetylcholine in the bladder. They act as an autocrine positive feedback loop and further increase release of acetylcholine. Antagonism of these receptors by imidafenacin prevents contraction of the bladder's detrusor muscle, prevents inhibition of the relation produced by sympathetic tone, and reduces acetylcholine release. Together these reduce the frequency of urination.
Target Actions Organism AMuscarinic acetylcholine receptor M1 antagonistHumans AMuscarinic acetylcholine receptor M2 antagonistHumans AMuscarinic acetylcholine receptor M3 antagonistHumans - Absorption
The absolute oral bioavailability is 57.8% 5. Tmax is 1-3 h after administration.
- Volume of distribution
The estimated volume of distribution is 43.9 L 5.
- Protein binding
Imidafenacin is 88% bounf by human plasma proteins 5. It binds to serum albumin and α1-acid glycoprotein.
- Metabolism
Thought to be metabolized v by CYP3A4 and UGT1A4 5. No active metabolites have been observed.
- Route of elimination
10% is excreted in the urine as the parent compound 5. Most is eliminated by metabolism thought to be mediated by CYP3A4 and UGT1A4.
- Half-life
The half life of elimination is 3 h 5.
- Clearance
The estimated clearance is 21.2 L/h 5.
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Clinically significant adverse reactions to imidafenacin are acute glaucoma (0.06%), urinary retention (0.03%), and heptic dysfunction (0.02%) Label. The most common adverse effects observed with imidafenacin are thirst (37.7%), constipation (13.6%).
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Imidafenacin which could result in a higher serum level. Abametapir The serum concentration of Imidafenacin can be increased when it is combined with Abametapir. Aceclofenac Aceclofenac may decrease the excretion rate of Imidafenacin which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Imidafenacin which could result in a higher serum level. Acetaminophen Acetaminophen may decrease the excretion rate of Imidafenacin which could result in a higher serum level. - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Staybla (Ono Pharmaceutical) / Uritos (Kyorin Pharmaceutical)
Categories
- ATC Codes
- G04BD14 — Imidafenacin
- Drug Categories
- Agents producing tachycardia
- Anticholinergic Agents
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Drugs for Urinary Frequency and Incontinence
- Drugs that are Mainly Renally Excreted
- Genito Urinary System and Sex Hormones
- Muscarinic Antagonists
- UGT1A4 substrates
- Urologicals
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Diphenylmethanes
- Direct Parent
- Diphenylmethanes
- Alternative Parents
- Phenylacetamides / N-substituted imidazoles / Fatty amides / Heteroaromatic compounds / Primary carboxylic acid amides / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives show 1 more
- Substituents
- Aromatic heteromonocyclic compound / Azacycle / Azole / Carbonyl group / Carboxamide group / Carboxylic acid derivative / Diphenylmethane / Fatty acyl / Fatty amide / Heteroaromatic compound show 12 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- XJR8Y07LJO
- CAS number
- 170105-16-5
- InChI Key
- SQKXYSGRELMAAU-UHFFFAOYSA-N
- InChI
- 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)
- IUPAC Name
- 4-(2-methyl-1H-imidazol-1-yl)-2,2-diphenylbutanamide
- SMILES
- CC1=NC=CN1CCC(C(N)=O)(C1=CC=CC=C1)C1=CC=CC=C1
References
- General References
- Kobayashi F, Yageta Y, Segawa M, Matsuzawa S: 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. Arzneimittelforschung. 2007;57(2):92-100. [Article]
- Miyachi H, Kiyota H, Uchiki H, Segawa M: Synthesis and antimuscarinic activity of a series of 4-(1-Imidazolyl)-2,2-diphenylbutyramides: discovery of potent and subtype-selective antimuscarinic agents. Bioorg Med Chem. 1999 Jun;7(6):1151-61. [Article]
- Kuraoka S, Ito Y, Wakuda H, Shinozuka K, Onoue S, Yamada S: Characterization of muscarinic receptor binding by the novel radioligand, [(3)H]imidafenacin, in the bladder and other tissues of rats. J Pharmacol Sci. 2016 Jul;131(3):184-9. doi: 10.1016/j.jphs.2016.06.002. Epub 2016 Jun 23. [Article]
- Chess-Williams R: Muscarinic receptors of the urinary bladder: detrusor, urothelial and prejunctional. Auton Autacoid Pharmacol. 2002 Jun;22(3):133-45. [Article]
- Ohno T, Nakade S, Nakayama K, Kitagawa J, Miyabe H, Konomi T, Miyata Y: Population pharmacokinetic analysis of a novel muscarinic receptor antagonist, imidafenacin, in healthy volunteers and overactive bladder patients. Drug Metab Pharmacokinet. 2008;23(6):456-63. [Article]
- External Links
- PubChem Compound
- 6433090
- PubChem Substance
- 310265160
- ChemSpider
- 4938278
- ChEBI
- 134720
- ChEMBL
- CHEMBL53366
- ZINC
- ZINC000000007368
- Wikipedia
- Imidafenacin
- FDA label
- Download (294 KB)
- MSDS
- Download (77.2 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data4 Completed Treatment Overactive Bladder Syndrome (OABS) 2 somestatus stop reason just information to hide 3 Completed Treatment Overactive Bladder Syndrome (OABS) 3 somestatus stop reason just information to hide 2 Completed Treatment Overactive Bladder Syndrome (OABS) 1 somestatus stop reason just information to hide Not Available Completed Not Available Overactive Bladder Syndrome (OABS) 2 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 0.100 mg Tablet, film coated Oral 0.1 mg Tablet Oral 0.1 mg Tablet, coated Oral 0.1 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00951 mg/mL ALOGPS logP 2.81 ALOGPS logP 2.76 Chemaxon logS -4.5 ALOGPS pKa (Strongest Acidic) 16.11 Chemaxon pKa (Strongest Basic) 7.35 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 60.91 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 94.86 m3·mol-1 Chemaxon Polarizability 35.03 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-07r4-8591000000-207c69b6c9d77434a717 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-00di-0359000000-5577d3a61859b86b81b5 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-004l-0794000000-1142cdff0109f9c2c7ef Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0097-0943000000-910458065c51dc277673 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-00kf-1910000000-4e97bba05a36990633d5 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-00kf-0920000000-9bb337e4ea0db34a211a Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0007-3900000000-2ac7e0c21e7a87751f2a Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 172.908 predictedDeepCCS 1.0 (2019) [M+H]+ 175.266 predictedDeepCCS 1.0 (2019) [M+Na]+ 182.3394 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover
- Specific Function
- G protein-coupled acetylcholine receptor activity
- Gene Name
- CHRM1
- Uniprot ID
- P11229
- Uniprot Name
- Muscarinic acetylcholine receptor M1
- Molecular Weight
- 51420.375 Da
References
- Kuraoka S, Ito Y, Wakuda H, Shinozuka K, Onoue S, Yamada S: Characterization of muscarinic receptor binding by the novel radioligand, [(3)H]imidafenacin, in the bladder and other tissues of rats. J Pharmacol Sci. 2016 Jul;131(3):184-9. doi: 10.1016/j.jphs.2016.06.002. Epub 2016 Jun 23. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol
- Specific Function
- Arrestin family protein binding
- Gene Name
- CHRM2
- Uniprot ID
- P08172
- Uniprot Name
- Muscarinic acetylcholine receptor M2
- Molecular Weight
- 51714.605 Da
References
- Kuraoka S, Ito Y, Wakuda H, Shinozuka K, Onoue S, Yamada S: Characterization of muscarinic receptor binding by the novel radioligand, [(3)H]imidafenacin, in the bladder and other tissues of rats. J Pharmacol Sci. 2016 Jul;131(3):184-9. doi: 10.1016/j.jphs.2016.06.002. Epub 2016 Jun 23. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover
- Specific Function
- Acetylcholine binding
- Gene Name
- CHRM3
- Uniprot ID
- P20309
- Uniprot Name
- Muscarinic acetylcholine receptor M3
- Molecular Weight
- 66127.445 Da
References
- Kuraoka S, Ito Y, Wakuda H, Shinozuka K, Onoue S, Yamada S: Characterization of muscarinic receptor binding by the novel radioligand, [(3)H]imidafenacin, in the bladder and other tissues of rats. J Pharmacol Sci. 2016 Jul;131(3):184-9. doi: 10.1016/j.jphs.2016.06.002. Epub 2016 Jun 23. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Ohno T, Nakade S, Nakayama K, Kitagawa J, Miyabe H, Konomi T, Miyata Y: Population pharmacokinetic analysis of a novel muscarinic receptor antagonist, imidafenacin, in healthy volunteers and overactive bladder patients. Drug Metab Pharmacokinet. 2008;23(6):456-63. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:18177842, PubMed:24641623). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:18177842). Involved in the glucuronidation of calcidiol, which is the major circulating form of vitamin D3 essential for the regulation of calcium and phosphate homeostasis (PubMed:24641623). Also glucuronidates the biologically active form of vitamin D3, calcitriol, probably leading to its biliary transport and intestinal reabsorption (PubMed:18177842)
- Specific Function
- Enzyme binding
- Gene Name
- UGT1A4
- Uniprot ID
- P22310
- Uniprot Name
- UDP-glucuronosyltransferase 1A4
- Molecular Weight
- 60024.535 Da
References
- Ohno T, Nakade S, Nakayama K, Kitagawa J, Miyabe H, Konomi T, Miyata Y: Population pharmacokinetic analysis of a novel muscarinic receptor antagonist, imidafenacin, in healthy volunteers and overactive bladder patients. Drug Metab Pharmacokinet. 2008;23(6):456-63. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- Antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- Ohno T, Nakade S, Nakayama K, Kitagawa J, Miyabe H, Konomi T, Miyata Y: Population pharmacokinetic analysis of a novel muscarinic receptor antagonist, imidafenacin, in healthy volunteers and overactive bladder patients. Drug Metab Pharmacokinet. 2008;23(6):456-63. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction
- Specific Function
- Not Available
Components:
References
- Ohno T, Nakade S, Nakayama K, Kitagawa J, Miyabe H, Konomi T, Miyata Y: Population pharmacokinetic analysis of a novel muscarinic receptor antagonist, imidafenacin, in healthy volunteers and overactive bladder patients. Drug Metab Pharmacokinet. 2008;23(6):456-63. [Article]
Drug created at October 26, 2015 17:45 / Updated at May 07, 2021 21:07