Identification

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Name
Metolazone
Accession Number
DB00524  (APRD01109)
Type
Small Molecule
Groups
Approved
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.

Structure
Thumb
Synonyms
  • 2-Methyl-3-o-tolyl-6-sulfamyl-7-chloro-1,2,3,4-tetrahydro-4-quinazolinone
  • 7-Chloro-1,2,3,4-tetrahydro-2-methyl-3-(2-methylphenyl)-4-oxo-6-quinazolinesulfonamide
  • 7-Chloro-1,2,3,4-tetrahydro-2-methyl-4-oxo-3-o-tolyl-6-quinazolinesulfonamide
  • Metolazon
  • Metolazona
  • Métolazone
  • Metolazone
  • Metolazonum
External IDs
SR 720-22 / SR-720-22
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MetolazoneTablet5 mg/1OralH.j. Harkins Co., Inc.2017-12-08Not applicableUs
Mykrox TabletsTablet500 ug/1OralUNSPECIFIED2006-01-12Not applicableUs
ZaroxolynTablet5 mgOralAventis Pharma Ltd.1974-12-312003-07-22Canada
ZaroxolynTablet2.5 mg/1OralPhysicians Total Care, Inc.1973-11-272010-06-30Us
ZaroxolynTablet2.5 mgOralSanofi Aventis1974-12-31Not applicableCanada
ZaroxolynTablet5 mg/1OralPhysicians Total Care, Inc.1973-11-272012-06-30Us
ZaroxolynTablet2.5 mg/1OralCarilion Materials Management1973-11-27Not applicableUs
ZaroxolynTablet2.5 mg/1OralUnither Pharmaceuticals1973-11-272015-04-30Us
ZaroxolynTablet5 mg/1OralUnither Pharmaceuticals1973-11-272015-11-30Us
Zaroxolyn Tab 10mgTabletOralRhone Poulenc Rorer1974-12-311998-08-12Canada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MetolazoneTablet5 mg/1OralCardinal Health2011-01-142016-11-30Us
MetolazoneTablet5 mg/1OralUpstate Pharma, LLC1973-11-27Not applicableUs65580 0644 71 nlmimage10 08450428
MetolazoneTablet2.5 mg/1OralAvera McKennan Hospital2015-04-162018-06-07Us69189 064320180907 15195 mps9bu
MetolazoneTablet5 mg/1OralMajor Pharmaceuticals1973-11-27Not applicableUs
MetolazoneTablet10 mg/1OralPhysicians Total Care, Inc.2004-07-20Not applicableUs
MetolazoneTablet5 mg/1OralAphena Pharma Solutions - Tennessee, LLC2003-12-19Not applicableUs
MetolazoneTablet2.5 mg/1OralAphena Pharma Solutions - Tennessee, LLC1973-11-27Not applicableUs
MetolazoneTablet5 mg/1OralCarilion Materials Management2004-10-19Not applicableUs
MetolazoneTablet2.5 mg/1OralCardinal Health2011-01-142016-10-31Us
MetolazoneTablet2.5 mg/1OralUpstate Pharma, LLC1973-11-27Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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International/Other Brands
Diulo / Diurem (Cipla) / Metadure (Micro Labs) / Metenix (IFET) / Metolaz (Navana) / Metoral (Dr. Reddy's) / Metoz (Centaur) / Metozone (Ying Yuan) / Mykrox (Celltech) / Pavedal (Pharma Investi) / Xuret / Zytanix (Zydus)
Categories
UNII
TZ7V40X7VX
CAS number
17560-51-9
Weight
Average: 365.835
Monoisotopic: 365.06008979
Chemical Formula
C16H16ClN3O3S
InChI Key
AQCHWTWZEMGIFD-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

Pharmacology

Indication

For the treatment of hypertension, alone or in combination with other antihypertensive drugs of a different class.

Associated Conditions
Pharmacodynamics

Metolazone 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 action

The 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.

TargetActionsOrganism
ASolute carrier family 12 member 3
inhibitor
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

Peak blood levels are obtained within 2 to 4 hours of oral administration. The rate and extent of absorption are formulation dependent.

Volume of distribution
Not Available
Protein binding

50-70% 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 elimination

Most of the drug is excreted in the unconverted form in the urine.

Half life

Approximately 14 hours.

Clearance
Not Available
Toxicity

Symptoms 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
PathwayCategory
Metolazone Action PathwayDrug action
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.
DrugInteraction
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid may decrease the antihypertensive activities of Metolazone.
1-benzylimidazole1-benzylimidazole may decrease the antihypertensive activities of Metolazone.
1alpha-Hydroxyvitamin D5The risk or severity of hypokalemia can be increased when 1alpha-Hydroxyvitamin D5 is combined with Metolazone.
1alpha,24S-Dihydroxyvitamin D2The risk or severity of hypokalemia can be increased when 1alpha,24S-Dihydroxyvitamin D2 is combined with Metolazone.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Metolazone.
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the antihypertensive activities of Metolazone.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the antihypertensive activities of Metolazone.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the antihypertensive activities of Metolazone.
4-Methoxyamphetamine4-Methoxyamphetamine may decrease the antihypertensive activities of Metolazone.
5-methoxy-N,N-dimethyltryptamine5-methoxy-N,N-dimethyltryptamine may decrease the antihypertensive activities of Metolazone.
Additional Data Available
  • Extended Description
    Extended Description

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  • Severity
    Severity

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  • Evidence Level
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Food Interactions
  • Take with food to reduce gastric irritation.

References

General References
  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:16189620]
External Links
Human Metabolome Database
HMDB0014665
KEGG Drug
D00431
PubChem Compound
4170
PubChem Substance
46509058
ChemSpider
4026
BindingDB
25899
ChEBI
64354
ChEMBL
CHEMBL878
Therapeutic Targets Database
DAP000749
PharmGKB
PA164781022
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Metolazone
ATC Codes
C03EA12 — Metolazone and potassium-sparing agentsC03BA08 — MetolazoneG01AE10 — Combinations of sulfonamides
AHFS Codes
  • 40:28.24 — Thiazide-like Diuretics
FDA label
Download (834 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers3
1CompletedTreatmentCongestive Heart Failure / Prophylaxis of cardiomyopathy1
3Not Yet RecruitingTreatmentAcute Coronary Syndromes (ACS) / Ischaemic Heart Diseases / Revascularization1
3TerminatedTreatmentAcute Decompensated Heart Failure (ADHF)1
4Active Not RecruitingTreatmentAcute Heart Failure (AHF) / Fluid Overload1
4CompletedTreatmentHeart Failure1
4CompletedTreatmentRapid Ventricular Response Atrial Fibrillation1
4Enrolling by InvitationTreatmentAcute Heart Failure (AHF) / Cardiovascular Disease (CVD) / Heart Failure / Heart Failure With Reduced Ejection Fraction (HFrEF)1
4TerminatedTreatmentAcute Decompensated Heart Failure (ADHF)1
4Unknown StatusTreatmentCongestive Heart Failure1
Not AvailableWithdrawnTreatmentCongestive Heart Failure2
Not AvailableWithdrawnTreatmentHypernatremia / Respiratory Failure / Volume Overload1

Pharmacoeconomics

Manufacturers
  • Gd searle llc
  • Mylan pharmaceuticals inc
  • Roxane laboratories inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
  • Ucb inc
Packagers
  • Amerisource Health Services Corp.
  • Cardinal Health
  • Caremark LLC
  • Diversified Healthcare Services Inc.
  • Eon Labs
  • Mckesson Corp.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Pharmaceutical Utilization Management Program VA Inc.
  • Physicians Total Care Inc.
  • Prepackage Specialists
  • Resource Optimization and Innovation LLC
  • Sandhills Packaging Inc.
  • Southwood Pharmaceuticals
  • Teva Pharmaceutical Industries Ltd.
  • UCB Pharma
  • UDL Laboratories
  • Upstate Pharma LLC
  • Vangard Labs Inc.
Dosage forms
FormRouteStrength
TabletOral10 mg/1
TabletOral2.5 mg/1
TabletOral5 mg/1
TabletOral500 ug/1
TabletOral2.5 mg
TabletOral5 mg
TabletOral
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.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)256 °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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-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
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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0aor-1494000000-aae5f0a5c86e9d0828e2
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0bvi-2960000000-1eed022b28a6bb140f60

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazanaphthalenes
Sub Class
Benzodiazines
Direct Parent
Quinazolines
Alternative Parents
Toluenes / Secondary alkylarylamines / Organosulfonamides / Aryl chlorides / Vinylogous amides / Tertiary carboxylic acid amides / Aminosulfonyl compounds / Lactams / Amino acids and derivatives / Azacyclic compounds
show 5 more
Substituents
Quinazoline / Secondary aliphatic/aromatic amine / Toluene / Aryl chloride / Aryl halide / Monocyclic benzene moiety / Benzenoid / Organosulfonic acid amide / Organic sulfonic acid or derivatives / Vinylogous amide
show 22 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
sulfonamide, organochlorine compound, quinazolines (CHEBI:64354)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Key mediator of sodium and chloride reabsorption in this nephron segment, accounting for a significant fraction of renal sodium reabsorption.
Gene Name
SLC12A3
Uniprot ID
P55017
Uniprot Name
Solute carrier family 12 member 3
Molecular Weight
113138.04 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on June 13, 2005 07:24 / Updated on November 16, 2019 10:24