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targets (4) enzymes (1)
for drugs
Identification
Name Triamterene
Accession Number DB00384 (APRD00079)
Type small molecule
Groups approved
Description

A pteridine that is used as a mild diuretic. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Triamteren
Brand names
  • Ademin
  • Ademine
  • Diren
  • Ditak
  • Diucelpin
  • Diurene
  • Dyazide
  • Dyren
  • Dyrenium
  • Dytac
  • Jatropur
  • Maxzide
  • Maxzide-25
  • Noridil
  • Noridyl
  • Pterofen
  • Pterophene
  • Taturil
  • Teriam
  • Teridin
  • Tri-Span
  • Triampur
  • Triamteril
  • Triamteril Complex
  • Trispan
  • Triteren
  • Urocaudal
Brand name mixtures
  • Apo Triazide Tab (Hydrochlorothiazide + Triamterene)
  • Dyazide Tab (Hydrochlorothiazide + Triamterene)
  • Novo-Triamzide (Hydrochlorothiazide + Triamterene)
  • Nu-Triazide Tab 50 Mg/25 Mg (Hydrochlorothiazide + Triamterene)
  • Penta-Triamterene HCTZ Tablets (Hydrochlorothiazide + Triamterene)
  • Pro-Triazide (Hydrochlorothiazide + Triamterene)
  • Riva-Zide 50/25mg Tablets (Hydrochlorothiazide + Triamterene)
Categories
  • Diuretics
  • Potassium-sparing Diuretics
CAS number 396-01-0
Weight Average: 253.2626
Monoisotopic: 253.107593387
Chemical Formula C12H11N7
InChI Key InChIKey=FNYLWPVRPXGIIP-UHFFFAOYSA-N
InChI
InChI=1S/C12H11N7/c13-9-7(6-4-2-1-3-5-6)16-8-10(14)18-12(15)19-11(8)17-9/h1-5H,(H6,13,14,15,17,18,19)
Plain Text
IUPAC Name
6-phenylpteridine-2,4,7-triamine
SMILES
NC1=NC2=C(N=C(C3=CC=CC=C3)C(N)=N2)C(N)=N1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes
  • Pteridines
Substructures
  • Aliphatic and Aryl Amines
  • Benzene and Derivatives
  • Pyrimidines and Derivatives
  • Pyrazines
  • Heterocyclic compounds
  • Aromatic compounds
  • Pteridines
  • Imines
  • Cyanamides
Pharmacology
Indication 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.
Pharmacodynamics Triamterene, a relatively weak, potassium-sparing diuretic and antihypertensive, is used in the management of hypokalemia. Triamterene is similar in action to amiloride but, unlike amiloride, increases the urinary excretion of magnesium.
Mechanism of action Triamterene inhibits the epithelial sodium channels on principal cells in the late distal convoluted tubule and collecting tubule, which are responsible for 1-2% of total sodium reabsorption. As sodium reabsorption is inhibited, this increases the osmolarity in the nephron lumen and decreases the osmolarity of the interstitium. Since sodium concentration is the main driving force for water reabsorption, triamterene can achieve a modest amount of diuresis by decreasing the osmotic gradient necessary for water reabsorption from lumen to interstitium. Triamterene also has a potassium-sparing effect. Normally, the process of potassium excretion is driven by the electrochemical gradient produced by sodium reabsorption. As sodium is reabsorbed, it leaves a negative potential in the lumen, while producing a positive potential in the principal cell. This potential promotes potassium excretion through apical potassium channels. By inhibiting sodium reabsorption, triamterene also inhibits potassium excretion.
Absorption Rapidly absorbed, with somewhat less than 50% of the oral dose reaching the urine.
Volume of distribution Not Available
Protein binding 55-67% (93% for the OH-TA-ester metabolite)
Metabolism

Triamterene is primarily metabolized to the sulfate conjugate of hydroxytriamterene. Both the plasma and urine levels of this metabolite greatly exceed triamterene levels.
Route of elimination Not Available
Half life 255 minutes (188 minutes for OH-TA-ester metabolite) after IV administration.
Clearance
  • 4.5 l/min [total plasma clearance]
  • 0.22 l/kg [renal plasma clearance]
Toxicity In the event of overdosage it can be theorized that electrolyte imbalance would be the major concern, with particular attention to possible hyperkalemia. Other symptoms that might be seen would be nausea and vomiting, other G.I. disturbances, and weakness. It is conceivable that some hypotension could occur. The oral LD50 in mice is 380 mg/kg.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00132 Triamterene Pathway SMP00132
Pharmacoeconomics
Manufacturers
  • Wellspring pharmaceutical corp
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Prices Not Available
Patents Not Available
Properties
State solid
Melting point 316 oC
Experimental Properties
Property Value Source
water solubility 48.2 mg/L PhysProp
logP 0.3 PhysProp
Predicted Properties
Property Value Source
water solubility 9.63e-01 g/l ALOGPS
logP 1.21 ALOGPS
logP 1.11 ChemAxon Molconvert
logS -2.42 ALOGPS
pKa 18.53 ChemAxon Molconvert
hydrogen acceptor count 7 ChemAxon Molconvert
hydrogen donor count 3 ChemAxon Molconvert
polar surface area 129.62 ChemAxon Molconvert
rotatable bond count 1 ChemAxon Molconvert
refractivity 75.13 ChemAxon Molconvert
polarizability 25.90 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. WellSpring Pharmaceutical Corporation. Dyrenium (triamterene) capsules prescribing information. Neptune, NJ; 2001 June.
  2. Gilfrich HJ, Kremer G, Mohrke W, Mutschler E, Volger KD: Pharmacokinetics of triamterene after i.v. administration to man: determination of bioavailability. Eur J Clin Pharmacol. 1983;25(2):237-41. Pubmed
External Links
Resource Link
KEGG Drug D00386 Link_out
PubChem Compound 5546 Link_out
PubChem Substance 46507623 Link_out
ChemSpider 5345 Link_out
BindingDB 6644 Link_out
Therapeutic Targets Database DAP000575 Link_out
PharmGKB PA451752 Link_out
Drug Product Database 1919563 Link_out
RxList http://www.rxlist.com/cgi/generic/triamterine.htm Link_out
Drugs.com http://www.drugs.com/triamterene.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Triamterene Link_out
ATC Codes
  • C03DB02
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS show (73.5 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Amiloride-sensitive sodium channel subunit gamma

Pharmacological action: yes
Actions: inhibitor

Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. Also plays a role in taste perception

Organism class: human
UniProt ID: P51170 Link_out
Gene: SCNN1G Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Hiraoka Y, Taniguchi T, Tanaka T, Okada K, Kanamaru H, Muramatsu I: Pharmacological characterization of unique prazosin-binding sites in human kidney. Naunyn Schmiedebergs Arch Pharmacol. 2003 Jul;368(1):49-56. Epub 2003 Jun 25. Pubmed
  4. Busch AE, Suessbrich H, Kunzelmann K, Hipper A, Greger R, Waldegger S, Mutschler E, Lindemann B, Lang F: Blockade of epithelial Na+ channels by triamterenes – underlying mechanisms and molecular basis. Pflugers Arch. 1996 Sep;432(5):760-6. Pubmed
  5. Wagner CA, Ott M, Klingel K, Beck S, Melzig J, Friedrich B, Wild KN, Broer S, Moschen I, Albers A, Waldegger S, Tummler B, Egan ME, Geibel JP, Kandolf R, Lang F: Effects of the serine/threonine kinase SGK1 on the epithelial Na(+) channel (ENaC) and CFTR: implications for cystic fibrosis. Cell Physiol Biochem. 2001;11(4):209-18. Pubmed

2. Amiloride-sensitive sodium channel subunit alpha

Pharmacological action: yes
Actions: inhibitor

Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. Also plays a role in taste perception

Organism class: human
UniProt ID: P37088 Link_out
Gene: SCNN1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Busch AE, Suessbrich H, Kunzelmann K, Hipper A, Greger R, Waldegger S, Mutschler E, Lindemann B, Lang F: Blockade of epithelial Na+ channels by triamterenes – underlying mechanisms and molecular basis. Pflugers Arch. 1996 Sep;432(5):760-6. Pubmed
  4. Wagner CA, Ott M, Klingel K, Beck S, Melzig J, Friedrich B, Wild KN, Broer S, Moschen I, Albers A, Waldegger S, Tummler B, Egan ME, Geibel JP, Kandolf R, Lang F: Effects of the serine/threonine kinase SGK1 on the epithelial Na(+) channel (ENaC) and CFTR: implications for cystic fibrosis. Cell Physiol Biochem. 2001;11(4):209-18. Pubmed
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

3. Amiloride-sensitive sodium channel subunit beta

Pharmacological action: yes
Actions: inhibitor

Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. Also plays a role in taste perception

Organism class: human
UniProt ID: P51168 Link_out
Gene: SCNN1B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Busch AE, Suessbrich H, Kunzelmann K, Hipper A, Greger R, Waldegger S, Mutschler E, Lindemann B, Lang F: Blockade of epithelial Na+ channels by triamterenes – underlying mechanisms and molecular basis. Pflugers Arch. 1996 Sep;432(5):760-6. Pubmed
  4. Wagner CA, Ott M, Klingel K, Beck S, Melzig J, Friedrich B, Wild KN, Broer S, Moschen I, Albers A, Waldegger S, Tummler B, Egan ME, Geibel JP, Kandolf R, Lang F: Effects of the serine/threonine kinase SGK1 on the epithelial Na(+) channel (ENaC) and CFTR: implications for cystic fibrosis. Cell Physiol Biochem. 2001;11(4):209-18. Pubmed

4. Amiloride-sensitive sodium channel subunit delta

Pharmacological action: unknown
Actions: inhibitor

Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. Also plays a role in taste perception

Organism class: human
UniProt ID: P51172 Link_out
Gene: SCNN1D Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Wagner CA, Ott M, Klingel K, Beck S, Melzig J, Friedrich B, Wild KN, Broer S, Moschen I, Albers A, Waldegger S, Tummler B, Egan ME, Geibel JP, Kandolf R, Lang F: Effects of the serine/threonine kinase SGK1 on the epithelial Na(+) channel (ENaC) and CFTR: implications for cystic fibrosis. Cell Physiol Biochem. 2001;11(4):209-18. Pubmed
Enzymes

1. Cytochrome P450 1A2

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 26, 2010 17:23

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.