DT-Web

DB00524 - Metolazone


Identification
Name Metolazone
Accession Number DB00524 (APRD01109)
Type small molecule
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. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 365.835
Groups approved
Monoisotopic Weight 365.06008979
Pharmacology
Indication For the treatment of hypertension, alone or in combination with other antihypertensive drugs of a different class.
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.
Absorption Peak blood levels are obtained within 2 to 4 hours of oral administration. The rate and extent of absorption are formulation dependent.
Protein binding 50-70% bound to erythrocytes, up to 33% bound to plasma proteins, 2-5% of the drug in circulation is unbound
Biotransformation 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.
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
Interactions
Drug Interactions
Drug Mechanism of interaction
Deslanoside Possible electrolyte variations and arrhythmias
Digitoxin Possible electrolyte variations and arrhythmias
Digoxin Possible electrolyte variations and arrhythmias
Dofetilide Increased risk of cardiotoxicity and arrhythmias
Lithium The thiazide diuretic, metolazone, may increase serum levels of lithium.
Tenoxicam Tenoxicam may antagonize the blood pressure lowering effect of Metolazone. Monitor for changes in the therapeutic effect of Metolazone if Tenoxicam is initiated, discontinued or dose changed.
Trandolapril The thiazide diuretic, Metolazone, may increase the hypotensive effect of Trandolapril. Metolazone may also increase the nephrotoxicity of Trandolapril. Monitor for postural hypotension at initiation of concomitant therapy and renal dysfunction during chronic therapy.
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Food Interactions
  • Take with food to reduce gastric irritation.

Targets


Solute carrier family 12 member 3
Name Solute carrier family 12 member 3
Gene Name SLC12A3
Pharmacological action yes
Actions inhibitor
References
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.6195

Predictions


Id Partner name Gene Name Score
295 Carbonic anhydrase 1 CA1 0.1244
357 Carbonic anhydrase 2 CA2 0.0897
592 Carbonic anhydrase 4 CA4 0.0881
610 Calcium-activated potassium channel subunit alpha 1 KCNMA1 0.0638
3007 Carbonic anhydrase 12 CA12 0.0507
4205 Carbonic anhydrase 9 CA9 0.0507
310 Solute carrier family 12 member 2 SLC12A2 0.0361
558 Solute carrier family 12 member 1 SLC12A1 0.0283
1729 Solute carrier family 22 member 6 SLC22A6 0.0263
1405 Thiopurine S-methyltransferase TPMT 0.0258
781 ATP-sensitive inward rectifier potassium channel 11 KCNJ11 0.0205
3426 Glutamine synthetase glnA 0.0198
3987 Glutamine synthetase GLUL 0.0198
806 Sodium/potassium-transporting ATPase alpha-1 chain ATP1A1 0.0181
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