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Identification
NameTriamterene
Accession NumberDB00384  (APRD00079)
Typesmall molecule
Groupsapproved
Description

A pteridine that is used as a mild diuretic. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
6-phenylpteridine-2,4,7-triamineNot AvailableIUPAC
TeridinNot AvailableIS
TriamterenGermanINN
TriamtérèneFrenchDCF
TriamtereneNot AvailableUSAN, JAN, DCIT, BAN, BP 2011, JP XV, Ph. Eur. 7, USP 34
TriamterenoSpanishINN
TriamterenumLatinPh. Eur. 7
SaltsNot Available
Brand names
NameCompany
DiuterenKotobuki Seiyaku
DyazideGoldshield
DyreniumWellspring
DytacMercury
RiyazineCiiphar
TriterenKyoto Yakuhin
UrinisYing Yuan
Brand mixtures
Brand NameIngredients
DyazideHydrochlorothiazide + Triamterene
MaxzideHydrochlorothiazide + Triamterene
Nu-TriazideHydrochlorothiazide + Triamterene
Penta-Triamterene HCTZHydrochlorothiazide + Triamterene
Pro-TriazideHydrochlorothiazide + Triamterene
Riva-ZideHydrochlorothiazide + Triamterene
TriampurHydrochlorothiazide + Triamterene
Categories
CAS number396-01-0
WeightAverage: 253.2626
Monoisotopic: 253.107593387
Chemical FormulaC12H11N7
InChI KeyInChIKey=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)
IUPAC Name
6-phenylpteridine-2,4,7-triamine
SMILES
NC1=NC(N)=C2N=C(C(N)=NC2=N1)C1=CC=CC=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassPteridines and Derivatives
SubclassNot Available
Direct parentPteridines and Derivatives
Alternative parentsAminopyrimidines and Derivatives; Pyrazines; Primary Aromatic Amines; Benzene and Substituted Derivatives; Polyamines
Substituentsaminopyrimidine; benzene; pyrimidine; primary aromatic amine; pyrazine; polyamine; primary amine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the pteridines and derivatives. These are polycyclic aromatic compounds containing a pteridine moiety, which consists of a pyrimidine fused to a pyrazine ring to form pyrimido(4,5-b)pyrazine.
Pharmacology
IndicationFor 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.
PharmacodynamicsTriamterene, 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 actionTriamterene 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.
AbsorptionRapidly absorbed, with somewhat less than 50% of the oral dose reaching the urine.
Volume of distributionNot Available
Protein binding55-67% (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 eliminationNot Available
Half life255 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]
ToxicityIn 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.8735
Caco-2 permeable + 0.7017
P-glycoprotein substrate Non-substrate 0.6269
P-glycoprotein inhibitor I Non-inhibitor 0.8782
P-glycoprotein inhibitor II Non-inhibitor 0.8814
Renal organic cation transporter Non-inhibitor 0.8437
CYP450 2C9 substrate Non-substrate 0.8949
CYP450 2D6 substrate Non-substrate 0.8892
CYP450 3A4 substrate Non-substrate 0.7542
CYP450 1A2 substrate Inhibitor 0.9107
CYP450 2C9 substrate Non-inhibitor 0.907
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.831
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6161
Ames test Non AMES toxic 0.8934
Carcinogenicity Non-carcinogens 0.9092
Biodegradation Not ready biodegradable 0.9959
Rat acute toxicity 2.7706 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9604
hERG inhibition (predictor II) Non-inhibitor 0.6829
Pharmacoeconomics
Manufacturers
  • Wellspring pharmaceutical corp
Packagers
Dosage forms
FormRouteStrength
CapsuleOral
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point316 °CPhysProp
water solubility48.2 mg/LNot Available
logP0.98HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
water solubility9.63e-01 g/lALOGPS
logP1.21ALOGPS
logP1.11ChemAxon
logS-2.4ALOGPS
pKa (strongest acidic)15.88ChemAxon
pKa (strongest basic)3.11ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count7ChemAxon
hydrogen donor count3ChemAxon
polar surface area129.62ChemAxon
rotatable bond count1ChemAxon
refractivity75.13ChemAxon
polarizability25.9ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
Spectra
References
Synthesis Reference

Frederic J. Nugent, John K. C. Yen, “Process for preparing the combination products of triamterene and hydrochlorothiazide.” U.S. Patent US4804540, issued July, 1987.

US4804540
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
ResourceLink
KEGG DrugD00386
PubChem Compound5546
PubChem Substance46507623
ChemSpider5345
BindingDB6644
Therapeutic Targets DatabaseDAP000575
PharmGKBPA451752
IUPHAR4329
Guide to Pharmacology4329
Drug Product Database1919563
RxListhttp://www.rxlist.com/cgi/generic/triamterine.htm
Drugs.comhttp://www.drugs.com/triamterene.html
WikipediaTriamterene
ATC CodesC03DB02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(73.5 KB)
Interactions
Drug Interactions
Drug
BenazeprilIncreased risk of hyperkalemia
CandesartanIncreased risk of hyperkalemia
CaptoprilIncreased risk of hyperkalemia
CilazaprilIncreased risk of hyperkalemia
DrospirenoneIncreased risk of hyperkalemia
EnalaprilIncreased risk of hyperkalemia
EplerenoneThis association presents an increased risk of hyperkalemia
EprosartanIncreased risk of hyperkalemia
ForasartanIncreased risk of hyperkalemia
FosinoprilIncreased risk of hyperkalemia
IndomethacinRisk of acute renal impairment with this combination
IrbesartanIncreased risk of hyperkalemia
LisinoprilIncreased risk of hyperkalemia
LosartanIncreased risk of hyperkalemia
MoexiprilIncreased risk of hyperkalemia
PerindoprilIncreased risk of hyperkalemia
Polystyrene sulfonateAntagonism of action
PotassiumIncreased risk of hyperkalemia
QuinaprilIncreased risk of hyperkalemia
RamiprilIncreased risk of hyperkalemia
SaprisartanIncreased risk of hyperkalemia
SpiraprilIncreased risk of hyperkalemia
TasosartanIncreased risk of hyperkalemia
TelmisartanTelmisartan may increase the hyperkalemic effect of Triamterene. Monitor for increased serum potassium concentrations during concomitant therapy.
TrandolaprilIncreased risk of hyperkalemia. Monitor serum potassium levels.
TreprostinilAdditive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
ValsartanIncreased risk of hyperkalemia
Food InteractionsNot Available

1. Amiloride-sensitive sodium channel subunit gamma

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Amiloride-sensitive sodium channel subunit gamma P51170 Details

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Amiloride-sensitive sodium channel subunit alpha P37088 Details

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Amiloride-sensitive sodium channel subunit beta P51168 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Amiloride-sensitive sodium channel subunit delta P51172 Details

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

1. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

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 January 12, 2014 21:01