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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=CC(Cl)=C(C=C2C(=O)N1C3=C(C)C=CC=C3)S(N)(=O)=O

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

Molecular Formula C16H16ClN3O3S
Molecular Weight 365.835
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

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

Targets

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ZAROXOLYN
Primary
ZAROXOLYN

Cmax

ValueDoseCo-administeredAnalytePopulation
8.225 ng/mL
0.5 mg single, oral
METOLAZONE plasma
Homo sapiens
3.63 ng/mL
2.5 mg 1 times / day unknown, oral
METOLAZONE unknown
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
50.51 ng × h/mL
0.5 mg single, oral
METOLAZONE plasma
Homo sapiens
99.74 ng × h/mL
2.5 mg 1 times / day unknown, oral
METOLAZONE unknown
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
7.47 h
0.5 mg single, oral
METOLAZONE plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
7.5%
2.5 mg 1 times / day unknown, oral
METOLAZONE unknown
Homo sapiens

Doses

AEs

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​

Tox targets

PubMed

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%
Substance Class Chemical
Record UNII
TZ7V40X7VX
Record Status Validated (UNII)
Record Version