Identification

Name
Flavoxate
Accession Number
DB01148  (APRD00972)
Type
Small Molecule
Groups
Approved
Description

A drug that has been used in various urinary syndromes and as an antispasmodic. Its therapeutic usefulness and its mechanism of action are not clear. It may have local anesthetic activity and direct relaxing effects on smooth muscle as well as some activity as a muscarinic antagonist. [PubChem]

Structure
Thumb
Synonyms
  • 2-(1-Piperidinyl)ethyl 3-methyl-4-oxo-2-phenyl-4H-chromene-8-carboxylate
  • 2-Piperidinoethyl 3-methyl-4-oxo-2-phenyl-4H-1-benzopyran-8-carboxylate
  • 2-Piperidinoethyl 3-methylflavone-8-carboxylate
  • beta-Piperidinoethyl 3-methylflavone-8-carboxylate
  • Flavoxate
  • Flavoxate HCI
  • Flavoxato
  • Flavoxatum
Product Ingredients
IngredientUNIICASInChI Key
Flavoxate Hydrochloride9C05J6089W3717-88-2XOEVKNFZUQEERE-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FlavoxateTablet200 mgOralPharmel Inc1998-02-162016-10-26Canada
UrispasTablet, film coated100 mg/1OralAlza1970-01-152009-03-30Us
Urispas Tab 200mgTablet200 mgOralCedona Pharmaceuticals B.V.1986-12-312009-07-28Canada
Urispas Tab 200mgTablet200 mgOralPaladin Labs Inc1987-12-31Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-flavoxateTablet200 mgOralApotex Corporation2001-11-20Not applicableCanada
Flavoxate HydrochlorideTablet100 mg/1OralEpic Pharma, LLC2011-02-21Not applicableUs42806 0058 01 nlmimage10 a14a50e2
Flavoxate HydrochlorideTablet100 mg/1OralGolden State Medical Supply2011-02-212018-09-27Us
Flavoxate HydrochlorideTablet100 mg/1OralPuraCap Laboratories LLC dba Blu Pharmaceuticals2016-12-15Not applicableUs
Flavoxate HydrochlorideTablet, film coated100 mg/1OralCarilion Materials Management2004-12-22Not applicableUs
Flavoxate HydrochlorideTablet, film coated100 mg/1OralPaddock Laboratories, LLC2004-12-22Not applicableUs
Flavoxate HydrochlorideTablet, film coated100 mg/1OralTAGI Pharma, Inc.2011-03-25Not applicableUs
Flavoxate HydrochlorideTablet, film coated100 mg/1OralPhysicians Total Care, Inc.2012-01-04Not applicableUs54868 632620180907 15195 1nbwjw
Flavoxate HydrochlorideTablet100 mg/1OralAv Pak2012-11-30Not applicableUs
Flavoxate HydrochlorideTablet, film coated100 mg/1OralImpax Generics2003-08-282016-12-09Us00115 1811 01 nlmimage10 ff07ffef
International/Other Brands
Bladuril (Sanofi) / Flavosert (Daito) / Progut (Sanwa Kagaku) / Sawadaron (Sawai Seiyaku) / Uridron (Johnson) / Uripax (Farmindustria) / Urispas (Adcock Ingram Pharmaceuticals) / Uroxal (Sandoz)
Categories
UNII
3E74Y80MEY
CAS number
15301-69-6
Weight
Average: 391.4596
Monoisotopic: 391.178358293
Chemical Formula
C24H25NO4
InChI Key
SPIUTQOUKAMGCX-UHFFFAOYSA-N
InChI
InChI=1S/C24H25NO4/c1-17-21(26)19-11-8-12-20(23(19)29-22(17)18-9-4-2-5-10-18)24(27)28-16-15-25-13-6-3-7-14-25/h2,4-5,8-12H,3,6-7,13-16H2,1H3
IUPAC Name
2-(piperidin-1-yl)ethyl 3-methyl-4-oxo-2-phenyl-4H-chromene-8-carboxylate
SMILES
CC1=C(OC2=C(C=CC=C2C(=O)OCCN2CCCCC2)C1=O)C1=CC=CC=C1

Pharmacology

Indication

For symptomatic relief of dysuria, urgency, nocturia, suprapubic pain, frequency and incontinence as may occur in cystitis, prostatitis, urethritis, urethrocystitis/urethrotrigonitis.

Associated Conditions
Pharmacodynamics

Flavoxate is a spasmolytic flavone derivative that acts by relaxing the smooth muscle in the urinary tract. Flavoxate is a competitive muscarinic receptor antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. Muscarinic receptors play an important role in several major cholin-ergically mediated functions, including contractions of urinary bladder smooth muscle and stimulation of salivary secretion.

Mechanism of action

Flavoxate acts as a direct antagonist at muscarinic acetylcholine receptors in cholinergically innervated organs. Its anticholinergic-parasympatholytic action reduces the tonus of smooth muscle in the bladder, effectively reducing the number of required voids, urge incontinence episodes, urge severity and improving retention, facilitating increased volume per void.

TargetActionsOrganism
AMuscarinic acetylcholine receptor M2
antagonist
Human
AMuscarinic acetylcholine receptor M1
antagonist
Human
Absorption

Well absorbed from gastrointestinal tract.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination

57% of the flavoxate HCl was excreted in the urine within 24 hours.

Half life
Not Available
Clearance
Not Available
Toxicity

The oral LD50 for flavoxate HCl in rats is 4273 mg/kg. The oral LD50 for flavoxate HCl in mice is 1837 mg/kg. Symptoms of overdose include convulsions, decreased ability to sweat, (warm, red skin, dry mouth, and increased body temperature), hallucinations, increased heart rate and blood pressure, and mental confusion.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1,10-PhenanthrolineThe therapeutic efficacy of Flavoxate can be decreased when used in combination with 1,10-Phenanthroline.
AbacavirAbacavir may decrease the excretion rate of Flavoxate which could result in a higher serum level.
AcarboseAcarbose may decrease the excretion rate of Flavoxate which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Flavoxate which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Flavoxate which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Flavoxate which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Flavoxate which could result in a higher serum level.
AclidiniumThe risk or severity of adverse effects can be increased when Flavoxate is combined with Aclidinium.
AcrivastineFlavoxate may decrease the excretion rate of Acrivastine which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Flavoxate which could result in a higher serum level.
Food Interactions
  • Food may reduce irritation.
  • Take without regard to meals.

References

Synthesis Reference

Da Re, P.; U.S. Patent 2,921,070; January 12, 1960; assigned to Recordati-Laboratorio Farmacologico SPA, Italy.

General References
Not Available
External Links
Human Metabolome Database
HMDB0015279
KEGG Compound
C07809
PubChem Compound
3354
PubChem Substance
46505138
ChemSpider
3237
ChEBI
5088
ChEMBL
CHEMBL1493
Therapeutic Targets Database
DAP001114
PharmGKB
PA164781386
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Flavoxate
ATC Codes
G04BD02 — Flavoxate
AHFS Codes
  • 86:12.04 — Antimuscarinics
MSDS
Download (241 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHealthy Volunteers1
4CompletedTreatmentPain NOS1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Alza Corp.
  • Cardinal Health
  • Catalent Pharma Solutions
  • Global Pharmaceuticals
  • Kaiser Foundation Hospital
  • McNeil Laboratories
  • Mikart Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Neuman Distributors Inc.
  • Ortho Mcneil Janssen Pharmaceutical Inc.
  • Paddock Labs
  • PD-Rx Pharmaceuticals Inc.
Dosage forms
FormRouteStrength
TabletOral100 mg/1
Tablet, film coatedOral100 mg/1
TabletOral200 mg
Prices
Unit descriptionCostUnit
Urispas 100 mg tablet1.79USD tablet
Flavoxate hcl 100 mg tablet1.49USD tablet
Apo-Flavoxate 200 mg Tablet0.76USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)232-234U.S. Patent 2,921,070
water solubility10 mg/L (at 37 °C)MERCK INDEX (1996)
logP4.4Not Available
pKa7.3MERCK INDEX (1996)
Predicted Properties
PropertyValueSource
Water Solubility0.0154 mg/mLALOGPS
logP3.65ALOGPS
logP4.24ChemAxon
logS-4.4ALOGPS
pKa (Strongest Basic)7.29ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area55.84 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity113.51 m3·mol-1ChemAxon
Polarizability43.39 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9851
Blood Brain Barrier+0.9505
Caco-2 permeable+0.5421
P-glycoprotein substrateSubstrate0.7553
P-glycoprotein inhibitor IInhibitor0.7986
P-glycoprotein inhibitor IIInhibitor0.8388
Renal organic cation transporterInhibitor0.5166
CYP450 2C9 substrateNon-substrate0.8398
CYP450 2D6 substrateNon-substrate0.6898
CYP450 3A4 substrateSubstrate0.5522
CYP450 1A2 substrateInhibitor0.9106
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorInhibitor0.796
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6708
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.9323
BiodegradationNot ready biodegradable0.8989
Rat acute toxicity2.2772 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.6988
hERG inhibition (predictor II)Non-inhibitor0.6137
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as flavones. These are flavonoids with a structure based on the backbone of 2-phenylchromen-4-one (2-phenyl-1-benzopyran-4-one).
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Flavonoids
Sub Class
Flavones
Direct Parent
Flavones
Alternative Parents
Chromones / Pyranones and derivatives / Piperidines / Benzene and substituted derivatives / Heteroaromatic compounds / Trialkylamines / Carboxylic acid esters / Amino acids and derivatives / Oxacyclic compounds / Monocarboxylic acids and derivatives
show 5 more
Substituents
Flavone / Chromone / Benzopyran / 1-benzopyran / Pyranone / Monocyclic benzene moiety / Piperidine / Pyran / Benzenoid / Heteroaromatic compound
show 18 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
piperidines, tertiary amino compound, carboxylic ester, flavones (CHEBI:5088)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
G-protein coupled acetylcholine receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM2
Uniprot ID
P08172
Uniprot Name
Muscarinic acetylcholine receptor M2
Molecular Weight
51714.605 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Greco KA, McVary KT: The role of combination medical therapy in benign prostatic hyperplasia. Int J Impot Res. 2008 Dec;20 Suppl 3:S33-43. doi: 10.1038/ijir.2008.51. [PubMed:19002123]
  4. Uckert S, Stief CG, Odenthal KP, Truss MC, Lietz B, Jonas U: Responses of isolated normal human detrusor muscle to various spasmolytic drugs commonly used in the treatment of the overactive bladder. Arzneimittelforschung. 2000 May;50(5):456-60. [PubMed:10858873]
  5. Abbiati GA, Ceserani R, Nardi D, Pietra C, Testa R: Receptor binding studies of the flavone, REC 15/2053, and other bladder spasmolytics. Pharm Res. 1988 Jul;5(7):430-3. [PubMed:3247311]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Abbiati GA, Ceserani R, Nardi D, Pietra C, Testa R: Receptor binding studies of the flavone, REC 15/2053, and other bladder spasmolytics. Pharm Res. 1988 Jul;5(7):430-3. [PubMed:3247311]

Drug created on June 13, 2005 07:24 / Updated on December 10, 2018 06:10