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Identification
NameMetolazone
Accession NumberDB00524  (APRD01109)
TypeSmall Molecule
GroupsApproved
Description

A quinazoline-sulfonamide that is considered a thiazide-like diuretic which is long-acting so useful in chronic renal failure. It also tends to lower blood pressure and increase potassium loss. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
2-Methyl-3-O-tolyl-6-sulfamyl-7-chloro-1,2,3,4-tetrahydro-4-quinazolinoneNot AvailableNot Available
7-Chloro-1,2,3,4-tetrahydro-2-methyl-3-(2-methylphenyl)-4-oxo-6-quinazolinesulfonamideNot AvailableNot Available
7-Chloro-1,2,3,4-tetrahydro-2-methyl-4-oxo-3-O-tolyl-6-quinazolinesulfonamideNot AvailableNot Available
MetolazonGermanINN
MetolazonaSpanishINN
MétolazoneFrenchINN
MetolazonumLatinINN
ZaroxolynNot AvailableNot Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Zaroxolyntablet5 mgoralUNITHER Manufacturing LLC1973-11-27Not AvailableUs
Zaroxolyntablet2.5 mgoralUNITHER Manufacturing LLC1973-11-27Not AvailableUs
Metolazonetablet2.5 mgoralUpstate Pharma, LLC1973-11-27Not AvailableUs
Metolazonetablet5 mgoralUpstate Pharma, LLC1973-11-27Not AvailableUs
Metolazonetablet10 mgoralUpstate Pharma, LLC1973-11-27Not AvailableUs
Zaroxolyntablet2.5 mgoralCarilion Materials Management1973-11-27Not AvailableUs
Zaroxolyntablet2.5 mgoralSanofi Aventis Canada IncNot AvailableNot AvailableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Metolazonetablet5 mgoralEon Labs, Inc.2003-12-19Not AvailableUs
Metolazonetablet2.5 mgoralEon Labs, Inc.2003-12-19Not AvailableUs
Metolazonetablet10 mgoralEon Labs, Inc.2003-12-19Not AvailableUs
Metolazonetablet2.5 mgoralMylan Pharmaceuticals Inc.2004-01-06Not AvailableUs
Metolazonetablet5 mgoralMylan Pharmaceuticals Inc.2004-10-19Not AvailableUs
Metolazonetablet10 mgoralMylan Pharmaceuticals Inc.2004-10-19Not AvailableUs
Metolazonetablet2.5 mgoralNcs Health Care Of Ky, Inc Dba Vangard Labs2003-12-19Not AvailableUs
Metolazonetablet5 mgoralNcs Health Care Of Ky, Inc Dba Vangard Labs2003-12-19Not AvailableUs
Metolazonetablet2.5 mgoralNcs Health Care Of Ky, Inc Dba Vangard Labs2010-01-18Not AvailableUs
Metolazonetablet5 mgoralNcs Health Care Of Ky, Inc Dba Vangard Labs2010-01-18Not AvailableUs
Metolazonetablet2.5 mgoralMylan Institutional Inc.2005-04-15Not AvailableUs
Metolazonetablet5 mgoralMylan Institutional Inc.2005-02-01Not AvailableUs
Metolazonetablet5 mgoralPhysicians Total Care, Inc.2004-04-27Not AvailableUs
Metolazonetablet2.5 mgoralPhysicians Total Care, Inc.2004-07-06Not AvailableUs
Metolazonetablet10 mgoralPhysicians Total Care, Inc.2004-07-20Not AvailableUs
Metolazonetablet2.5 mgoralCardinal Health2011-01-14Not AvailableUs
Metolazonetablet5 mgoralCardinal Health2011-01-14Not AvailableUs
Metolazonetablet5 mgoralMc Kesson Packaging Services A Business Unit Of Mc Kesson Corporation2006-11-15Not AvailableUs
Metolazonetablet2.5 mgoralAmerican Health Packaging2010-10-04Not AvailableUs
Metolazonetablet5 mgoralAmerican Health Packaging2010-10-04Not AvailableUs
Metolazonetablet10 mgoralCarilion Materials Management2004-10-19Not AvailableUs
Over the Counter ProductsNot Available
International Brands
NameCompany
DiuloNot Available
DiuremCipla
MetadureMicro Labs
MetenixIFET
MetolazNavana
MetoralDr. Reddy's
MetozCentaur
MetozoneYing Yuan
MykroxCelltech
PavedalPharma Investi
ZytanixZydus
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number17560-51-9
WeightAverage: 365.835
Monoisotopic: 365.06008979
Chemical FormulaC16H16ClN3O3S
InChI KeyAQCHWTWZEMGIFD-UHFFFAOYSA-N
InChI
InChI=1S/C16H16ClN3O3S/c1-9-5-3-4-6-14(9)20-10(2)19-13-8-12(17)15(24(18,22)23)7-11(13)16(20)21/h3-8,10,19H,1-2H3,(H2,18,22,23)
IUPAC Name
7-chloro-2-methyl-3-(2-methylphenyl)-4-oxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide
SMILES
CC1NC2=CC(Cl)=C(C=C2C(=O)N1C1=CC=CC=C1C)S(N)(=O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as quinazolines. These are compounds containing a quinazoline moiety, which is made up of two fused six-member aromatic rings, a benzene ring and a pyrimidine ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassNaphthyridines
Sub ClassQuinazolines
Direct ParentQuinazolines
Alternative Parents
Substituents
  • Quinazoline
  • Aminotoluene
  • Toluene
  • Secondary aliphatic/aromatic amine
  • Benzenoid
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl chloride
  • Vinylogous amide
  • Aminosulfonyl compound
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • Tertiary amine
  • Lactam
  • Carboxamide group
  • Azacycle
  • Secondary amine
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of hypertension, alone or in combination with other antihypertensive drugs of a different class.
PharmacodynamicsMetolazone is a quinazoline diuretic, with properties generally similar to the thiazide diuretics. A proximal action of metolazone has been shown in humans by increased excretion of phosphate and magnesium ions and by a markedly increased fractional excretion of sodium in patients with severely compromised glomerular filtration. This action has been demonstrated in animals by micropuncture studies.
Mechanism of actionThe actions of metolazone result from interference with the renal tubular mechanism of electrolyte reabsorption. Metolazone acts primarily to inhibit sodium reabsorption at the cortical diluting site and to a lesser extent in the proximal convoluted tubule. Sodium and chloride ions are excreted in approximately equivalent amounts. The increased delivery of sodium to the distal tubular exchange site results in increased potassium excretion. Metolazone does not inhibit carbonic anhydrase. The antihypertensive mechanism of action of metolazone is not fully understood but is presumed to be related to its saluretic and diuretic properties.
AbsorptionPeak blood levels are obtained within 2 to 4 hours of oral administration. The rate and extent of absorption are formulation dependent.
Volume of distributionNot Available
Protein binding50-70% bound to erythrocytes, up to 33% bound to plasma proteins, 2-5% of the drug in circulation is unbound
Metabolism

Not substantially metabolized. 70-95% is excreted unchanged in urine via glomerular filtration and active tubular secretion. Undergoes enterohepatic recycling.

Route of eliminationMost of the drug is excreted in the unconverted form in the urine.
Half lifeApproximately 14 hours.
ClearanceNot Available
ToxicitySymptoms of overdose include difficulty breathing, dizziness, dizziness on standing up, drowsiness, fainting, irritation of the stomach and intestines, and lethargy leading to coma.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Metolazone Action PathwayDrug actionSMP00105
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9972
Blood Brain Barrier+0.5944
Caco-2 permeable-0.8957
P-glycoprotein substrateNon-substrate0.7578
P-glycoprotein inhibitor INon-inhibitor0.8113
P-glycoprotein inhibitor IINon-inhibitor0.5921
Renal organic cation transporterNon-inhibitor0.9223
CYP450 2C9 substrateNon-substrate0.6466
CYP450 2D6 substrateNon-substrate0.8279
CYP450 3A4 substrateNon-substrate0.579
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 substrateNon-inhibitor0.907
CYP450 2D6 substrateNon-inhibitor0.923
CYP450 2C19 substrateNon-inhibitor0.9025
CYP450 3A4 substrateNon-inhibitor0.831
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5788
Ames testNon AMES toxic0.8234
CarcinogenicityNon-carcinogens0.7193
BiodegradationNot ready biodegradable0.9961
Rat acute toxicity1.8955 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9922
hERG inhibition (predictor II)Non-inhibitor0.8735
Pharmacoeconomics
Manufacturers
  • Gd searle llc
  • Mylan pharmaceuticals inc
  • Roxane laboratories inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
  • Ucb inc
Packagers
Dosage forms
FormRouteStrength
Tabletoral10 mg
Tabletoral2.5 mg
Tabletoral5 mg
Prices
Unit descriptionCostUnit
Zaroxolyn 10 mg tablet2.89USD tablet
Zaroxolyn 5 mg tablet2.75USD tablet
Metolazone 10 mg tablet1.8USD tablet
Zaroxolyn 2.5 mg tablet1.74USD tablet
Metolazone 5 mg tablet1.51USD tablet
Metolazone 2.5 mg tablet1.37USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point256 °CPhysProp
water solubility60.3 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP2.5Not Available
logS-3.78ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.0407 mg/mLALOGPS
logP3.21ALOGPS
logP2.94ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)9.54ChemAxon
pKa (Strongest Basic)-1.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area92.5 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity94.59 m3·mol-1ChemAxon
Polarizability36.38 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Rosenberg J, Gustafsson F, Galatius S, Hildebrandt PR: Combination therapy with metolazone and loop diuretics in outpatients with refractory heart failure: an observational study and review of the literature. Cardiovasc Drugs Ther. 2005 Aug;19(4):301-6. Pubmed
External Links
ATC CodesC03BA08
AHFS Codes
  • 40:28.24
PDB EntriesNot Available
FDA labelDownload (834 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
DeslanosidePossible electrolyte variations and arrhythmias
DigitoxinPossible electrolyte variations and arrhythmias
DigoxinPossible electrolyte variations and arrhythmias
DofetilideIncreased risk of cardiotoxicity and arrhythmias
LithiumThe thiazide diuretic, metolazone, may increase serum levels of lithium.
TenoxicamTenoxicam may antagonize the blood pressure lowering effect of Metolazone. Monitor for changes in the therapeutic effect of Metolazone if Tenoxicam is initiated, discontinued or dose changed.
TrandolaprilThe thiazide diuretic, Metolazone, may increase the hypotensive effect of Trandolapril. Metolazone may also increase the nephrotoxicity of Trandolapril. Monitor for postural hypotension at initiation of concomitant therapy and renal dysfunction during chronic therapy.
TreprostinilAdditive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Food Interactions
  • Take with food to reduce gastric irritation.

Targets

1. Solute carrier family 12 member 3

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 12 member 3 P55017 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on February 04, 2014 21:27