Identification
- Summary
Metolazone is a thiazide-like diuretic used to treat hypertension.
- Brand Names
- Mykrox, Zaroxolyn
- Generic Name
- Metolazone
- DrugBank Accession Number
- DB00524
- Background
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.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Metolazone (DB00524)
- Weight
- Average: 365.835
Monoisotopic: 365.06008979 - Chemical Formula
- C16H16ClN3O3S
- 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
Pharmacology
- Indication
For the treatment of hypertension, alone or in combination with other antihypertensive drugs of a different class.
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 Management of Edema •••••••••••• Management of Edema •••••••••••• Used in combination to manage High blood pressure (hypertension) •••••••••••• •••••• Management of High blood pressure (hypertension) •••••••••••• Management of Mild hypertension •••••••••••• - Contraindications & Blackbox Warnings
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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 inhibitorHumans - 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
- Adverse Effects
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Symptoms of overdose include difficulty breathing, dizziness, dizziness on standing up, drowsiness, fainting, irritation of the stomach and intestines, and lethargy leading to coma.
- Pathways
Pathway Category Metolazone Action Pathway Drug action - Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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 Metolazone may increase the excretion rate of Abacavir which could result in a lower serum level and potentially a reduction in efficacy. Abaloparatide The risk or severity of adverse effects can be increased when Metolazone is combined with Abaloparatide. Acarbose The therapeutic efficacy of Acarbose can be decreased when used in combination with Metolazone. Acebutolol Metolazone may increase the hypotensive activities of Acebutolol. Aceclofenac The therapeutic efficacy of Metolazone can be decreased when used in combination with Aceclofenac. - Food Interactions
- Take with food. Food reduces irritation.
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.- Product Images
- 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)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Metolazone Tablet 5 mg/1 Oral H.j. Harkins Co., Inc. 2017-12-08 Not applicable US 
Mykrox Tablets Tablet 500 ug/1 Oral UNSPECIFIED 2006-01-12 Not applicable US Zaroxolyn Tablet 2.5 mg Oral Sanofi Aventis 1974-12-31 Not applicable Canada 
Zaroxolyn Tablet 2.5 mg/1 Oral Unither Pharmaceuticals 1973-11-27 2015-04-30 US Zaroxolyn Tablet 5 mg/1 Oral Physicians Total Care, Inc. 1973-11-27 2012-06-30 US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Metolazone Tablet 5 mg/1 Oral Major Pharmaceuticals 2020-12-02 Not applicable US Metolazone Tablet 5 mg/1 Oral Carilion Materials Management 2004-10-19 Not applicable US Metolazone Tablet 5 mg/1 Oral Major Pharmaceuticals 2023-08-30 Not applicable US Metolazone Tablet 5 mg/1 Oral Alembic Pharmaceuticals Limited 2020-12-02 Not applicable US Metolazone Tablet 10 mg/1 Oral Lannett Company, Inc. 1973-11-27 2024-01-31 US
Categories
- ATC Codes
- C03EA12 — Metolazone and potassium-sparing agents
- C03EA — Low-ceiling diuretics and potassium-sparing agents
- C03E — DIURETICS AND POTASSIUM-SPARING AGENTS IN COMBINATION
- C03 — DIURETICS
- C — CARDIOVASCULAR SYSTEM
- G01AE — Sulfonamides
- G01A — ANTIINFECTIVES AND ANTISEPTICS, EXCL. COMBINATIONS WITH CORTICOSTEROIDS
- G01 — GYNECOLOGICAL ANTIINFECTIVES AND ANTISEPTICS
- G — GENITO URINARY SYSTEM AND SEX HORMONES
- Drug Categories
- Amides
- Antihypertensive Agents
- Antihypertensive Agents Indicated for Hypertension
- Cardiovascular Agents
- Diuretics
- Drugs that are Mainly Renally Excreted
- Genito Urinary System and Sex Hormones
- Gynecological Antiinfectives and Antiseptics
- Heterocyclic Compounds, Fused-Ring
- Hyperglycemia-Associated Agents
- Hypotensive Agents
- Increased Diuresis
- Low-Ceiling Diuretics and Potassium-Sparing Agents
- Low-Ceiling Diuretics, Excl. Thiazides
- Membrane Transport Modulators
- Natriuretic Agents
- Non Potassium Sparing Diuretics
- Quinazolines
- Quinazolinones
- Sodium Chloride Symporter Inhibitors
- Sulfonamides
- Sulfones
- Sulfur Compounds
- Thiazide-like Diuretic
- Chemical TaxonomyProvided by Classyfire
- 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
- Amine / Amino acid or derivatives / Aminosulfonyl compound / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Carboxamide group / Carboxylic acid derivative show 22 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- sulfonamide, organochlorine compound, quinazolines (CHEBI:64354)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- TZ7V40X7VX
- CAS number
- 17560-51-9
- 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
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. [Article]
- External Links
- Human Metabolome Database
- HMDB0014665
- KEGG Drug
- D00431
- PubChem Compound
- 4170
- PubChem Substance
- 46509058
- ChemSpider
- 4026
- BindingDB
- 25899
- 6916
- 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
- FDA label
- Download (834 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Chronic Heart Failure (CHF) / Congestive Heart Failure (CHF) / Diuretics Drug Reactions 1 4 Completed Treatment Heart Failure 1 4 Completed Treatment Rapid Ventricular Response Atrial Fibrillation 1 4 Not Yet Recruiting Treatment Acute Heart Failure (AHF) 1 4 Recruiting Treatment Acute Heart Failure (AHF) / Diuretic Resistance 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 10 mg - 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
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 190.8708226 predictedDarkChem Lite v0.1.0 [M-H]- 177.16985 predictedDeepCCS 1.0 (2019) [M+H]+ 190.8781226 predictedDarkChem Lite v0.1.0 [M+H]+ 179.52783 predictedDeepCCS 1.0 (2019) [M+Na]+ 191.2131226 predictedDarkChem Lite v0.1.0 [M+Na]+ 185.62099 predictedDeepCCS 1.0 (2019)
Targets
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- 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. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:55