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Details

Stereochemistry RACEMIC
Molecular Formula C16H16ClN3O3S
Molecular Weight 365.835
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of METOLAZONE

SMILES

CC1NC2=C(C=C(C(Cl)=C2)S(N)(=O)=O)C(=O)N1C3=CC=CC=C3C

InChI

InChIKey=AQCHWTWZEMGIFD-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Description

Metolazone is a thiazide-like diuretic marketed under the brand names Mykrox and Zaroxolyn. Zaroxolyn is indicated for the treatment of salt and water retention including: • Edema accompanying congestive heart failure; • Edema accompanying renal diseases including the nephrotic syndrome and states of diminished renal function. Zaroxolyn is also indicated for the treatment of hypertension, alone or in combination with other antihypertensive drugs of a different class. Metolazone is a quinazoline diuretic, with properties generally similar to the thiazide diuretics. 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. 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.

Originator

Approval Year

TargetsConditions
PubMed

PubMed

TitleDatePubMed
Severe electrolyte disturbances associated with metolazone and furosemide.
1978 Apr
Hypoplastic anemia associated with metolazone.
1979 Jul 13
Palpable acute necrotizing arteritis secondary to metolazone.
1982 Jul
Excessive potassium depletion with metolazone and furosemide.
1983 Jul-Aug
Use of a bioassay in healthy men to evaluate diuretic-spironolactone combinations.
1983 May
Case report: metolazone-associated hypercalcemia and acute pancreatitis.
1991 Oct
Vasculitis due to metolazone.
1991 Sep
Risk factors for the development and progression of dyslipidemia after heart transplantation.
2002 Apr 27
Diuretic resistance predicts mortality in patients with advanced heart failure.
2002 Jul
Determination of a Metolazone metabolite in human urine by high-performance liquid chromatography/diode-array detection, high-performance liquid chromatography/electrospray ionization mass spectrometry and gas chromatography/mass spectrometry.
2004
Pathophysiology of functional mutations of the thiazide-sensitive Na-Cl cotransporter in Gitelman disease.
2004 Aug
FI-chemiluminometric study of thiazides by on-line photochemical reaction.
2004 Nov 19
[The place of diuretics in the treatment of chronic heart failure. Part I].
2005
Combination therapy with metolazone and loop diuretics in outpatients with refractory heart failure: an observational study and review of the literature.
2005 Aug
Screening procedure for detection of diuretics and uricosurics and/or their metabolites in human urine using gas chromatography-mass spectrometry after extractive methylation.
2005 Aug
How much responsibility should heart failure nurses take?
2005 Mar 16
[Diuretic therapy in heart failure].
2006 Jan-Feb
Pre-dosing metolazone with loop diuretic combination regimens.
2006 Jan-Feb
Cardiomyopathy, familial dilated.
2006 Jul 13
Reported medication use in the neonatal intensive care unit: data from a large national data set.
2006 Jun
Affinity-defining domains in the Na-Cl cotransporter: a different location for Cl- and thiazide binding.
2006 Jun 23
Beneficial effects of metolazone in a rat model of preeclampsia.
2006 Sep
Determination of metolazone in human blood by liquid chromatography with electrospray ionization tandem mass spectrometry.
2007 Jan 1
The evaluation of the diuretic action of parenteral formulations of metolazone.
2007 Jan-Feb
Treatment of diuretic refractory pleural effusions with bevacizumab in four patients with primary systemic amyloidosis.
2007 May
Premenstrual syndrome.
2007 May 1
Vitamin C-induced hyperoxaluria causing reversible tubulointerstitial nephritis and chronic renal failure: a case report.
2007 Nov 27
The pK(a) Distribution of Drugs: Application to Drug Discovery.
2007 Sep 17
The renal cortical interstitium: morphological and functional aspects.
2008 Aug
Acute right ventricular failure in the setting of acute pulmonary embolism or chronic pulmonary hypertension: a detailed review of the pathophysiology, diagnosis, and management.
2008 Feb
Carbonic anhydrase inhibitors. Sulfonamide diuretics revisited--old leads for new applications?
2008 Jul 21
Non-healing painful ulcers in a patient with chronic kidney disease and role of sodium thiosulfate: a case report.
2008 Sep 23
How to use diuretics in heart failure.
2009 Dec
How 40 kilograms of fluid retention can be overlooked: two case reports.
2009 Jan 8
Effects of increased dose of diuretics on symptoms, weight, 6-minute walk distance, and echocardiographic measurements of left ventricular systolic and diastolic function in 51 patients with symptomatic heart failure caused by reduced left ventricular ejection fraction treated with beta blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers.
2009 Jan-Feb
Drugs associated with more suicidal ideations are also associated with more suicide attempts.
2009 Oct 2
Characterizing environmental and phenotypic associations using information theory and electronic health records.
2009 Sep 17
Advances in systolic heart failure.
2010 Apr 27
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.
2010 Dec
Clinical effectiveness of telmisartan alone or in combination therapy for controlling blood pressure and vascular risk in the elderly.
2010 Dec 3
Cardio-renal syndromes: report from the consensus conference of the acute dialysis quality initiative.
2010 Mar
A single residue in transmembrane domain 11 defines the different affinity for thiazides between the mammalian and flounder NaCl transporters.
2010 Nov
Improved outcomes with early collaborative care of ambulatory heart failure patients discharged from the emergency department.
2010 Nov 2
Screening of a chemical library reveals novel PXR-activating pharmacologic compounds.
2015 Jan 5
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.
2015 May 18
Patents

Patents

Sample Use Guides

In Vivo Use Guide
Usual Adult Dose for Hypertension Initial dose: 2.5 mg orally once a day (Zaroxolyn) or 0.5 mg orally once a day (Mykrox). Usual Adult Dose for Edema Initial dose: 5 mg orally once a day (Zaroxolyn) or 0.5 mg orally once a day (Mykrox).
Route of Administration: Oral
In Vitro Use Guide
In flounder bladder, metolazone (100 uM) is the most potent of the thiazide diuretics, inhibiting 22Na+ uptake by Na+-Cl- cotransport by ~90%
Name Type Language
METOLAZONE
EP   HSDB   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN   INN  
Official Name English
METOLAZONE [EP]
Common Name English
SR-720-22
Code English
METOLAZONE [VANDF]
Common Name English
OLDREN
Brand Name English
7-CHLORO-1,2,3,4-TETRAHYDRO-2-METHYL-4-OXO-3-O-TOLYL-6-QUINAZOLINESULFONAMIDE
Common Name English
METOZALONE
Common Name English
METOLAZONE [USP-RS]
Common Name English
METOLAZONE [USAN]
Common Name English
METOLAZONE [ORANGE BOOK]
Common Name English
MYKROX
Brand Name English
METOLAZONE [JAN]
Common Name English
ZAROXOLYN
Brand Name English
METOLAZONE [MART.]
Common Name English
METENIX
Brand Name English
NORMELAN
Brand Name English
XURET
Brand Name English
METOLAZONE [INN]
Common Name English
6-QUINAZOLINESULFONAMIDE, 7-CHLORO-1,2,3,4-TETRAHYDRO-2-METHYL-3-(2-METHYLPHENYL)-4-OXO-
Systematic Name English
METOLAZONE [WHO-DD]
Common Name English
SR 720-22
Code English
METOLAZONE [HSDB]
Common Name English
METOLAZONE [MI]
Common Name English
METOLAZONE [USP]
Common Name English
METAZOLINE
Common Name English
DIULO
Brand Name English
Classification Tree Code System Code
LIVERTOX 630
Created by admin on Tue Oct 22 00:35:29 UTC 2019 , Edited by admin on Tue Oct 22 00:35:29 UTC 2019
WHO-ATC C03BA08
Created by admin on Tue Oct 22 00:35:29 UTC 2019 , Edited by admin on Tue Oct 22 00:35:29 UTC 2019
WHO-VATC QC03BA08
Created by admin on Tue Oct 22 00:35:29 UTC 2019 , Edited by admin on Tue Oct 22 00:35:29 UTC 2019
NDF-RT N0000175359
Created by admin on Tue Oct 22 00:35:29 UTC 2019 , Edited by admin on Tue Oct 22 00:35:29 UTC 2019
WHO-ATC C03EA12
Created by admin on Tue Oct 22 00:35:29 UTC 2019 , Edited by admin on Tue Oct 22 00:35:29 UTC 2019
NCI_THESAURUS C49185
Created by admin on Tue Oct 22 00:35:29 UTC 2019 , Edited by admin on Tue Oct 22 00:35:29 UTC 2019
WHO-VATC QC03EA12
Created by admin on Tue Oct 22 00:35:29 UTC 2019 , Edited by admin on Tue Oct 22 00:35:29 UTC 2019
NDF-RT N0000175420
Created by admin on Tue Oct 22 00:35:29 UTC 2019 , Edited by admin on Tue Oct 22 00:35:29 UTC 2019
Code System Code Type Description
WIKIPEDIA
METOLAZONE
Created by admin on Tue Oct 22 00:35:29 UTC 2019 , Edited by admin on Tue Oct 22 00:35:29 UTC 2019
PRIMARY
EVMPD
SUB08906MIG
Created by admin on Tue Oct 22 00:35:29 UTC 2019 , Edited by admin on Tue Oct 22 00:35:29 UTC 2019
PRIMARY
ChEMBL
CHEMBL878
Created by admin on Tue Oct 22 00:35:29 UTC 2019 , Edited by admin on Tue Oct 22 00:35:29 UTC 2019
PRIMARY
EPA CompTox
17560-51-9
Created by admin on Tue Oct 22 00:35:29 UTC 2019 , Edited by admin on Tue Oct 22 00:35:29 UTC 2019
PRIMARY
HSDB
17560-51-9
Created by admin on Tue Oct 22 00:35:29 UTC 2019 , Edited by admin on Tue Oct 22 00:35:29 UTC 2019
PRIMARY
INN
2627
Created by admin on Tue Oct 22 00:35:29 UTC 2019 , Edited by admin on Tue Oct 22 00:35:29 UTC 2019
PRIMARY
ECHA (EC/EINECS)
241-539-3
Created by admin on Tue Oct 22 00:35:29 UTC 2019 , Edited by admin on Tue Oct 22 00:35:29 UTC 2019
PRIMARY
IUPHAR
4838
Created by admin on Tue Oct 22 00:35:29 UTC 2019 , Edited by admin on Tue Oct 22 00:35:29 UTC 2019
PRIMARY
CAS
17560-51-9
Created by admin on Tue Oct 22 00:35:29 UTC 2019 , Edited by admin on Tue Oct 22 00:35:29 UTC 2019
PRIMARY
NCI_THESAURUS
C650
Created by admin on Tue Oct 22 00:35:29 UTC 2019 , Edited by admin on Tue Oct 22 00:35:29 UTC 2019
PRIMARY
MERCK INDEX
M7494
Created by admin on Tue Oct 22 00:35:29 UTC 2019 , Edited by admin on Tue Oct 22 00:35:29 UTC 2019
PRIMARY Merck Index
LactMed
17560-51-9
Created by admin on Tue Oct 22 00:35:29 UTC 2019 , Edited by admin on Tue Oct 22 00:35:29 UTC 2019
PRIMARY
PUBCHEM
4170
Created by admin on Tue Oct 22 00:35:29 UTC 2019 , Edited by admin on Tue Oct 22 00:35:29 UTC 2019
PRIMARY
RXCUI
6916
Created by admin on Tue Oct 22 00:35:29 UTC 2019 , Edited by admin on Tue Oct 22 00:35:29 UTC 2019
PRIMARY RxNorm
DRUG BANK
DB00524
Created by admin on Tue Oct 22 00:35:29 UTC 2019 , Edited by admin on Tue Oct 22 00:35:29 UTC 2019
PRIMARY
MESH
D008788
Created by admin on Tue Oct 22 00:35:29 UTC 2019 , Edited by admin on Tue Oct 22 00:35:29 UTC 2019
PRIMARY