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

Similar Structures

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

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
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Metolazone	Tablet	5 mg/1	Oral	H.j. Harkins Co., Inc.	2017-12-08	Not applicable
Mykrox Tablets	Tablet	500 ug/1	Oral	UNSPECIFIED	2006-01-12	Not applicable
Zaroxolyn	Tablet	5 mg	Oral	Aventis Pharma Ltd.	1974-12-31	2003-07-22
Zaroxolyn	Tablet	2.5 mg/1	Oral	Physicians Total Care, Inc.	1973-11-27	2010-06-30
Zaroxolyn	Tablet	2.5 mg	Oral	Sanofi Aventis	1974-12-31	Not applicable
Zaroxolyn	Tablet	5 mg/1	Oral	Physicians Total Care, Inc.	1973-11-27	2012-06-30
Zaroxolyn	Tablet	2.5 mg/1	Oral	Carilion Materials Management	1973-11-27	Not applicable
Zaroxolyn	Tablet	2.5 mg/1	Oral	Unither Pharmaceuticals	1973-11-27	2015-04-30
Zaroxolyn	Tablet	5 mg/1	Oral	Unither Pharmaceuticals	1973-11-27	2015-11-30
Zaroxolyn Tab 10mg	Tablet		Oral	Rhone Poulenc Rorer	1974-12-31	1998-08-12

Additional Data Available

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

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

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Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
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Metolazone	Tablet	5 mg/1	Oral	Cardinal Health	2011-01-14	2016-11-30
Metolazone	Tablet	5 mg/1	Oral	Upstate Pharma, LLC	1973-11-27	Not applicable
Metolazone	Tablet	2.5 mg/1	Oral	Avera McKennan Hospital	2015-04-16	2018-06-07
Metolazone	Tablet	5 mg/1	Oral	Major Pharmaceuticals	1973-11-27	Not applicable
Metolazone	Tablet	10 mg/1	Oral	Physicians Total Care, Inc.	2004-07-20	Not applicable
Metolazone	Tablet	5 mg/1	Oral	Aphena Pharma Solutions - Tennessee, LLC	2003-12-19	Not applicable
Metolazone	Tablet	2.5 mg/1	Oral	Aphena Pharma Solutions - Tennessee, LLC	1973-11-27	Not applicable
Metolazone	Tablet	5 mg/1	Oral	Carilion Materials Management	2004-10-19	Not applicable
Metolazone	Tablet	2.5 mg/1	Oral	Cardinal Health	2011-01-14	2016-10-31
Metolazone	Tablet	2.5 mg/1	Oral	Upstate Pharma, LLC	1973-11-27	Not applicable

Additional Data Available

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

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.

Target	Actions	Organism
ASolute carrier family 12 member 3	inhibitor	Humans

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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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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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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

Pathway	Category
Metolazone Action Pathway	Drug 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.

Drug	Interaction
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1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid	1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid may decrease the antihypertensive activities of Metolazone.
1-benzylimidazole	1-benzylimidazole may decrease the antihypertensive activities of Metolazone.
1alpha-Hydroxyvitamin D5	The risk or severity of hypokalemia can be increased when 1alpha-Hydroxyvitamin D5 is combined with Metolazone.
1alpha,24S-Dihydroxyvitamin D2	The risk or severity of hypokalemia can be increased when 1alpha,24S-Dihydroxyvitamin D2 is combined with Metolazone.
2,4-thiazolidinedione	The therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Metolazone.
2,5-Dimethoxy-4-ethylamphetamine	2,5-Dimethoxy-4-ethylamphetamine may decrease the antihypertensive activities of Metolazone.
2,5-Dimethoxy-4-ethylthioamphetamine	2,5-Dimethoxy-4-ethylthioamphetamine may decrease the antihypertensive activities of Metolazone.
4-Bromo-2,5-dimethoxyamphetamine	4-Bromo-2,5-dimethoxyamphetamine may decrease the antihypertensive activities of Metolazone.
4-Methoxyamphetamine	4-Methoxyamphetamine may decrease the antihypertensive activities of Metolazone.
5-methoxy-N,N-dimethyltryptamine	5-methoxy-N,N-dimethyltryptamine may decrease the antihypertensive activities of Metolazone.

Additional Data Available

Extended Description

Extended description of the mechanism of action and particular properties of each drug interaction.

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Severity

A severity rating for each drug interaction, from minor to major.

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Evidence Level

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Action

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Food Interactions

Take with food to reduce gastric irritation.

References

General References

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 agents

C03BA08 — Metolazone

G01AE10 — Combinations of sulfonamides

AHFS Codes

40:28.24 — Thiazide-like Diuretics

FDA label

Download (834 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
1	Completed	Not Available	Healthy Volunteers	3
1	Completed	Treatment	Congestive Heart Failure / Prophylaxis of cardiomyopathy	1
3	Not Yet Recruiting	Treatment	Acute Coronary Syndromes (ACS) / Ischaemic Heart Diseases / Revascularization	1
3	Terminated	Treatment	Acute Decompensated Heart Failure (ADHF)	1
4	Active Not Recruiting	Treatment	Acute Heart Failure (AHF) / Fluid Overload	1
4	Completed	Treatment	Heart Failure	1
4	Completed	Treatment	Rapid Ventricular Response Atrial Fibrillation	1
4	Enrolling by Invitation	Treatment	Acute Heart Failure (AHF) / Cardiovascular Disease (CVD) / Heart Failure / Heart Failure With Reduced Ejection Fraction (HFrEF)	1
4	Terminated	Treatment	Acute Decompensated Heart Failure (ADHF)	1
4	Unknown Status	Treatment	Congestive Heart Failure	1
Not Available	Withdrawn	Treatment	Congestive Heart Failure	2
Not Available	Withdrawn	Treatment	Hypernatremia / Respiratory Failure / Volume Overload	1

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

Form	Route	Strength
Tablet	Oral	10 mg/1
Tablet	Oral	2.5 mg/1
Tablet	Oral	5 mg/1
Tablet	Oral	500 ug/1
Tablet	Oral	2.5 mg
Tablet	Oral	5 mg
Tablet	Oral

Prices

Unit description	Cost	Unit
Zaroxolyn 10 mg tablet	2.89USD	tablet
Zaroxolyn 5 mg tablet	2.75USD	tablet
Metolazone 10 mg tablet	1.8USD	tablet
Zaroxolyn 2.5 mg tablet	1.74USD	tablet
Metolazone 5 mg tablet	1.51USD	tablet
Metolazone 2.5 mg tablet	1.37USD	tablet

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	256 °C	PhysProp
water solubility	60.3 mg/L (at 25 °C)	YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP	2.5	Not Available
logS	-3.78	ADME Research, USCD

Predicted Properties

Property	Value	Source
Water Solubility	0.0407 mg/mL	ALOGPS
logP	3.21	ALOGPS
logP	2.94	ChemAxon
logS	-4	ALOGPS
pKa (Strongest Acidic)	9.54	ChemAxon
pKa (Strongest Basic)	-1.6	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	92.5 Å²	ChemAxon
Rotatable Bond Count	2	ChemAxon
Refractivity	94.59 m³·mol^-1	ChemAxon
Polarizability	36.38 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	No	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	+	0.9972
Blood Brain Barrier	+	0.5944
Caco-2 permeable	-	0.8957
P-glycoprotein substrate	Non-substrate	0.7578
P-glycoprotein inhibitor I	Non-inhibitor	0.8113
P-glycoprotein inhibitor II	Non-inhibitor	0.5921
Renal organic cation transporter	Non-inhibitor	0.9223
CYP450 2C9 substrate	Non-substrate	0.6466
CYP450 2D6 substrate	Non-substrate	0.8279
CYP450 3A4 substrate	Non-substrate	0.579
CYP450 1A2 substrate	Non-inhibitor	0.9045
CYP450 2C9 inhibitor	Non-inhibitor	0.907
CYP450 2D6 inhibitor	Non-inhibitor	0.923
CYP450 2C19 inhibitor	Non-inhibitor	0.9025
CYP450 3A4 inhibitor	Non-inhibitor	0.831
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.5788
Ames test	Non AMES toxic	0.8234
Carcinogenicity	Non-carcinogens	0.7193
Biodegradation	Not ready biodegradable	0.9961
Rat acute toxicity	1.8955 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9922
hERG inhibition (predictor II)	Non-inhibitor	0.8735

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
LC-MS/MS Spectrum - LC-ESI-qTof , Positive	LC-MS/MS	Not Available
LC-MS/MS Spectrum - LC-ESI-qTof , Positive	LC-MS/MS	Not Available
MS/MS Spectrum - , positive	LC-MS/MS	splash10-0aor-1494000000-aae5f0a5c86e9d0828e2
MS/MS Spectrum - , positive	LC-MS/MS	splash10-0bvi-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
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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

Details1. Solute carrier family 12 member 3

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

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

Metolazone

Identification

Structure for Metolazone (DB00524)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References