General
Preferred name
TRIAMTERENE
Synonyms
Triamterene D5 ()
SKF8542 ()
Ademine ()
Triamterene396-01-0 ()
Triamterene ()
Triamterene-d5 ()
NSC-639359 ()
SK&F-8542 ()
Dyrenium ()
NSC-77625 ()
SK&F 8542 ()
SK-8542 ()
Dytac ()
P&D ID
PD002107
CAS
396-01-0
1189922-23-3
Tags
natural product
drug
available
Approved by
FDA
First approval
1964
Drug indication
Diuretic
Congestive heart failure
Edema
Hypertension
Drug Status
approved
Max Phase
4.0
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
PHARMACODYNAMICS
Triamterene, a relatively weak, potassium-sparing diuretic and antihypertensive, is used in the management of hypertension and edema. It primarily works on the distal nephron in the kidneys; it acts from the late distal tubule to the collecting duct to inhibit Na+ reabsorption and decreasing K+ excretion.[T28] As triamterene tends to conserve potassium more strongly than promoting Na+ excretion, it can cause an increase in serum potassium, which may result in hyperkalemia potentially associated with cardiac irregularities.[Label] In healthy volunteers administered with oral triamterene, there was an increase in the renal clearnace of sodium and magnesium, and a decrease in the clearance of uric acid and creatinine[A178039] due to its effect of reducing glomerular filtration renal plasma flow.[L6169] Triamterene does not affect calcium excretion.[L6169] In clinical trials, the use of triamterene in combination with hydrochlorothiazide resulted an enhanced blood pressure-lowering effects of hydrochlorothiazide.[A178048]
INDICATION
Triamterene is indicated for the treatment of edema associated with congestive heart failure, cirrhosis of the liver, and the nephrotic syndrome; also in steroid-induced edema, idiopathic edema, and edema due to secondary hyperaldosteronism.[Label]; ; Triamterene in combination with hydrochlorothiazide is indicated for the managment of hypertension or treatment of edema in patients who develop hypokalemia following hydrochlorothiazide monotherapy, and in patients who require thiazide diuretic and in whom the development of hypokalemia cannot be risked.[L6169] Triamterene allows the maintenance of potassium balance when given in combination with loop diuretics and thiazides.[T28]
ROE
Triamterene and its metabolites are excreted by the kidney by filtration and tubular secretion.[L6193] Upon oral ingestion, somewhat less than 50% of the oral dose reaches the urine. [Label] About 20% of an oral dose appears unchanged in the urine, 70% as the sulphate ester of hydroxytriamterene and 10% as free hydroxytriamterene and triamterene glucuronide. [L6193]
TOXICITY
Acute oral LD50 of triamterene in rats is 400 mg/kg and 285-380 mg/kg in mice.[Label,MSDS] There has been a case of reversible acute renal failure following ingestion of 50 combination pills containing 50 mg triamterene and 25 mg hydrochlorothiazide. [Label] Symptoms of overdose, such as nausea, vomiting, gastrointestinal disturbances, weakness, and hypotension, are related to electrolyte imbalances, such as hyperkalemia.[Label] As there is no specific antidote, emesis and gastric lavage should be use to induce immediate evacuation of the stomach and careful evaluation of the electrolyte pattern and fluid balance should be made.[Label] Dialysis may be somewhat effective in case of an overdosage.[Label]; ; In a carciongenicity study in male and female mice administered with triamterene at the highst dosage level, there was an increased incidence of hepatocellular neoplasia, primarily adenomas. However, this was not a dose-dependent phenomenon and there was no statistically significant difference from control incidence at any dose level.[Label] In bacterial assays, there was no demonstrated mutagenic potential of triamterene. In in vitro assay using Chinese hamster ovary (CHO) cells with or without metabolic activation, there were no chromosomal aberrations.[Label] Studies evaluating the effects of triamterene on reproductive system or fertility have not been conducted. It is advised that the use of triamterene is avoided during pregnancy. As triamterene has been detected in human breast milk, triamterene should be used when nursing is ceased.[Label]
HALF-LIFE
The half-life of the drug in plasma ranges from 1.5 to 2 hours.[L6193] In a pharmacokinetic study involving healthy volunteers, the terminal half-lives for triamterene and 4â²-hydroxytriamterene sulfate were 255 ± 42 and 188 ± 70 minutes, respectively, after intravenous infusion of the parent drug.[A577,L6163]
DESCRIPTION
Triamterene is a potassium-sparing diuretic.
(GtoPdb)
MOA
Triamterene inhibits the epithelial sodium channels (ENaC) located on the lumenal side in the late distal convoluted tubule and collecting tubule [A178042], which are transmembrane channels that normally promotes sodium uptake and potassium secretion.[A178048] In the late distal tubule to the collecting duct, sodium ions are actively reabsorbed via ENaC on the lumnial membrane and are extruded out of the cell into the peritubular medium by a sodium-potassium exchange pump, the Na-K-ATPase,[A178054] with water following passively.[T28] Triamterene exerts a diuretic effect on the distal renal tubule to inhibit the reabsorption of sodium ions in exchange for potassium and hydrogen ions and its natriuretic activity is limited by the amount of sodium reaching its site of action.[L6169] Its action is antagonistic to that of adrenal mineralocorticoids, such as aldosterone, but it is not an inhibitor or antagonist of aldosterone.[Label] Triamterene maintains or increases the sodium excretionm, thereby increasing the excretion of water, and reduces the excess loss of potassium, hydrogen and chloride ions by inhibiting the distal tubular exchange mechanism.[L6169] Due to its diuretic effect, triamterene rapidly and reversibly reduces the lumen-negative transepithelial potential difference by almost complete abolition of Na+ conductance without altering K+ conductance.[A177988] This reduces the driving force for potassium movement into the tubular lumen and thus decreases potassium excretion. [A178054] Triamterene is similar in action to [amiloride] but, unlike amiloride, increases the urinary excretion of magnesium.[A178039]
METABOLISM
Triamterene undergoes phase I metabolism involving hydroxylation, via CYP1A2 activity, to form 4'-hydroxytriamterene. 4'-Hydroxytriamterene is further transformed in phase II metabolism mediated by cytosolic sulfotransferases to form the major metabolite, 4â²-hydroxytriamterene sulfate, which retains a diuretic activity. [A39120,L6163] Both the plasma and urine levels of this metabolite greatly exceed triamterene levels [Label] while the renal clearance of the sulfate conjugate was les than that of triamterene; this low renal clearance of the sulfate conjugate as compared with triamterene may be explained by the low unbound fraction of the metabolite in plasma.[A178057]
ABSORPTION
Triamterene is shown to be rapidly absorbed in the gastrointestinal tract [T28] [Label] Its onset of action achiveved within 2 to 4 hours after oral ingestion [Label] and its duration of action is 12-16 hours.[T28] It is reported that the diuretic effect of triamterene may not be observed for several days after administration.[Label] In a pharmacokinetic study, the oral bioavailability of triamterene was determined to be 52%.[A178012] Following administration of a single oral dose to fasted healthy male volunteers, the mean AUC of triamterene was about 148.7 ng*hr/mL [L6169] and the mean peak plasma concentrations (Cmax) were 46.4 ng/mL reached at 1.1 hour after administration.[L6169] In a limited study, administration of triamterene in combination with hydrochlorothiazide resulted in an increased bioavailability of triamterene by about 67% and a delay of up to 2 hours in the absorption of the drug.[L6169] It is advised that triamterene is administered after meals; in a limited study, combination use of triamterene and hydrochlorothiazide with the consumption of a high-fat meal resulted in an increase in the mean bioavailability and peak serum concentrations of triamterene and its active sulfate metabolite, as well as a delay of up to 2 hours in the absorption of the active constituents.[L6169]
DESCRIPTION
Na+ channel blocker; diuretic
(LOPAC library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
1
Organisms
3
Compound Sets
31
CeMM library of unique drugs (CLOUD)
ChEMBL Approved Drugs
ChEMBL Drugs
Concise Guide to Pharmacology 2017/18
Concise Guide to Pharmacology 2019/20
Concise Guide to Pharmacology 2021/22
Concise Guide to Pharmacology 2023/24
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
DrugMatrix
Enamine BioReference Compounds
Guide to Pharmacology
JUMP-Target 1 Compound Set
LOPAC library
LSP-MoA library (Laboratory of Systems Pharmacology)
MedChem Express Bioactive Compound Library
NCATS Inxight Approved Drugs
NIH Clinical Collections (NCC)
NPC Screening Collection
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
The Spectrum Collection
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
42
Molecular Weight
253.11
Hydrogen Bond Acceptors
7
Hydrogen Bond Donors
3
Rotatable Bonds
1
Ring Count
3
Aromatic Ring Count
3
cLogP
0.83
TPSA
129.62
Fraction CSP3
0.0
Chiral centers
0.0
Largest ring
6.0
QED
0.59
Structural alerts
2
aggregator (Aggregator Advisor)
Aggregators
aggregator (ZINC)
Aggregators
Related compounds
Custom attributes
(extracted from source data)
Target
Sodium Channel
Amiloride-sensitive sodium channel, ENaC
ENaC
ENaC??S583
SCNN1A, SCNN1B, SCNN1D, SCNN1G
SCNN1G
G protein-coupled Bile Acid Receptor 1
Pathway
Membrane Transporter/Ion Channel
GPCR/G protein
MOA
amiloride-sensitive sodium channel inhibitor
Sodium Channel blocker
Indication
hypokalemia, hypertension, edema
Disease Area
endocrinology, cardiology
Therapeutic Class
Diuretics
Source data
