TRIAMTERENE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C12H11N7
Molecular Weight	253.2626
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NC2=C(N=C(C3=CC=CC=C3)C(N)=N2)C(N)=N1

InChI

InChIKey=FNYLWPVRPXGIIP-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00384
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/triamterene.html

Triamterene, a relatively weak, potassium-sparing diuretic and antihypertensive, is used in the management of hypokalemia. 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.Triamterene is used 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. Triamterene is maeketed under the trade name Dyrenium.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Amiloride-sensitive sodium channel, ENaC 4 Target ID: CHEMBL2107836 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5012f997-9fb2-4c3d-99fd-4f7efd7c39af https://www.ncbi.nlm.nih.gov/pubmed/6129855	Inhibitor 8504		5.0 µM [IC50]
Heart phosphodiesterase 2 Target ID: CHEMBL2111408 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6321204	Inhibitor 8504		127.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Edema associated with congestive heart failure 3 Sources: https://www.drugs.com/ppa/triamterene.html	Primary		Approved 8583	DYRENIUM Approved Use Edema: 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. Launch Date 1964

C_max

Value	Dose	Co-administered	Analyte	Population
44.77 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21193005	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		TRIAMTERENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
125.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7166735	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		TRIAMTERENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
46.4 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/016042s077lbl.pdf	37.5 mg 1 times / day multiple, oral dose: 37.5 mg route of administration: Oral experiment type: MULTIPLE co-administered: HYDROCHLOROTHIAZIDE	HYDROCHLOROTHIAZIDE	TRIAMTERENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
190.69 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21193005	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		TRIAMTERENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
488.4 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7166735	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		TRIAMTERENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
148.7 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/016042s077lbl.pdf	37.5 mg 1 times / day multiple, oral dose: 37.5 mg route of administration: Oral experiment type: MULTIPLE co-administered: HYDROCHLOROTHIAZIDE	HYDROCHLOROTHIAZIDE	TRIAMTERENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.75 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21193005	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		TRIAMTERENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2 h OTHER GOV https://www.medicines.org.uk/emc/medicine/28009#PHARMACOKINETIC_PROPS	unknown		TRIAMTERENE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
38.7% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7166735	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		TRIAMTERENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
33% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/016042s077lbl.pdf	37.5 mg 1 times / day multiple, oral dose: 37.5 mg route of administration: Oral experiment type: MULTIPLE co-administered: HYDROCHLOROTHIAZIDE	HYDROCHLOROTHIAZIDE	TRIAMTERENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
100 mg 2 times / day multiple, oral Dose: 100 mg, 2 times / day Route: oral Route: multiple Dose: 100 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6496322	unhealthy, 54 ± 3 years Health Status: unhealthy Age Group: 54 ± 3 years Sources: https://pubmed.ncbi.nlm.nih.gov/6496322	Other AEs: Kidney failure... Other AEs: Kidney failure (acute) Sources: https://pubmed.ncbi.nlm.nih.gov/6496322
37.5 mg 1 times / day single, oral Dose: 37.5 mg, 1 times / day Route: oral Route: single Dose: 37.5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/016042s079lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/016042s079lbl.pdf	Disc. AE: Hyperkalemia... AEs leading to discontinuation/dose reduction: Hyperkalemia Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/016042s079lbl.pdf

AEs

AE	Significance	Dose	Population
Kidney failure	acute	100 mg 2 times / day multiple, oral Dose: 100 mg, 2 times / day Route: oral Route: multiple Dose: 100 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6496322	unhealthy, 54 ± 3 years Health Status: unhealthy Age Group: 54 ± 3 years Sources: https://pubmed.ncbi.nlm.nih.gov/6496322
Hyperkalemia	Disc. AE	37.5 mg 1 times / day single, oral Dose: 37.5 mg, 1 times / day Route: oral Route: single Dose: 37.5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/016042s079lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/016042s079lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP1A2 1197 BCRP 697

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
BCRP 697	substrate 4014 Sources: https://dmd.aspetjournals.org/content/36/6/995 Page: 3.0	yes
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/16035375/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:9671	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:9671
ChemicalBook	CB0663775	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0663775
eMolecules	594844	https://www.emolecules.com/cgi-bin/more?vid=594844
MolPort	MolPort-001-641-070	https://www.molport.com/shop/molecule-link/MolPort-001-641-070
Selleck Chemicals	triamterene	http://www.selleckchem.com/products/triamterene.html
ZINC	ZINC000000120286	http://zinc15.docking.org/substances/ZINC000000120286

PubMed

Title	Date	PubMed
Irreversible renal failure associated with triamterene.	1991	1819215
[Simultaneous analysis of four diuretic drugs by HPLC and its application to health food supplements advertising weight reduction].	2002 Apr	12092419
Effects of anion and cation inhibitors and carbonic anhydrase inhibitors upon the activity of the gypsy moth (Lepidoptera: Lymantriidae) nucleo-polyhedrovirus.	2002 Apr	12019995
Screening for 18 diuretics and probenecid in doping analysis by liquid chromatography-tandem mass spectrometry.	2002 Dec	12474217
Determination of triamterene and its main metabolite hydroxytriamterene sulfate in human urine by capillary electrophoresis using ultraviolet absorbance and laser-induced fluorescence detection.	2002 Mar 25	11936683
Determination of triamterene by transitory retention in a continuous flow solid phase system with fluorimetric transduction.	2002 May 15	12008152
Micellar electrokinetic capillary chromatography analysis of diuretics in pharmaceutical formulations.	2002 May 16	18968622
Thiazide-induced lichenoid photosensitivity.	2002 Nov	12472543
Potentially significant drug interactions of class III antiarrhythmic drugs.	2003	12688833
Kinetic modeling of triamterene intestinal absorption and its inhibition by folic acid and methotrexate.	2003 May	14578108
Photostability studies on the furosemide-triamterene drug association.	2003 Sep	13679181
Drug-induced renal calculi: epidemiology, prevention and management.	2004	14871169
Treatment of congenital nephrogenic diabetes insipidus with hydrochlorothiazide and amiloride in an adult patient.	2004	14646392
Application of PLS regression to fluorimetric data for the determination of furosemide and triamterene in pharmaceutical preparations and triamterene in urine.	2004 Feb 6	18969296
Application of a fluorescence sensor for miniscale on-line monitoring of powder mixing kinetics.	2004 Jan	14648636
Effects of pH and the presence of micelles on the resolution of diuretics by reversed-phase liquid chromatography.	2004 Jan 2	14753771
Coil treatment of a fusiform upper basilar trunk aneurysm with a combination of "kissing" neuroform stents, TriSpan-, 3D- and fibered coils, and permanent implantation of the microguidewires.	2004 Jun	15103433
Triamterene-beta-cyclodextrin systems: preparation, characterization and in vivo evaluation.	2004 Mar 29	15198540
Use of the TriSpan coil to facilitate the transcatheter occlusion of pulmonary arteriovenous malformation.	2004 Nov-Dec	15593430
Dermatological conditions during TNF-alpha-blocking therapy in patients with rheumatoid arthritis: a prospective study.	2005	15899052
Differing effects of mineralocorticoid receptor-dependent and -independent potassium-sparing diuretics on fibrinolytic balance.	2005 Aug	15998706
Attenuation of the kaluretic properties of furosemide by triamterene (Dyrenium) in healthy volunteers.	2005 Feb	15726878
[Capillary electrophoresis with end-column electrochemical detection for hydrochlorothiazide and triamterene diuretics].	2005 Jan	15881361
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Capillary electrophoretic determination of triamterene, methotrexate, and creatinine in human urine.	2005 May	15912736
[Diuretic therapy in heart failure].	2006 Jan-Feb	16634001
[Influence of diuretics on occupationally important qualities of engine drivers].	2007	17354601
Fast quantitative determination of diuretic drugs in tablets and human urine by microchip electrophoresis with native fluorescence detection.	2007 Aug	17702070
Naturalised Vitis rootstocks in Europe and consequences to native wild grapevine.	2007 Jun 13	17565374
Update of diuretics in the treatment of hypertension.	2007 Mar-Apr	17414583
A study of western pharmaceuticals contained within samples of Chinese herbal/patent medicines collected from New York City's Chinatown.	2007 Sep	17652006
Determination of norfloxacin in rat liver perfusate using capillary electrophoresis with laser-induced fluorescence detection.	2007 Sep 1	17606416
Determination of losartan and triamterene in pharmaceutical compounds and urine using cathodic adsorptive stripping voltammetry.	2008	18997374
Practical aspects in the management of hypokalemic periodic paralysis.	2008 Apr 21	18426576
Development of a vessel-simulating flow-through cell method for the in vitro evaluation of release and distribution from drug-eluting stents.	2008 Aug 25	18562035
Evaluation of a neck-bridge device to assist endovascular treatment of wide-neck aneurysms of the anterior circulation.	2008 Jan	17928379
How long does it take to coil an intracranial aneurysm?	2008 Jan	17891386
Acute bilateral simultaneous angle closure glaucoma after topiramate administration: a case report.	2008 Jan 8	18182113
Chemical and genetic validation of dihydrofolate reductase-thymidylate synthase as a drug target in African trypanosomes.	2008 Jul	18557814
Quantitative investigation of the role of breast cancer resistance protein (Bcrp/Abcg2) in limiting brain and testis penetration of xenobiotic compounds.	2008 Jun	18322075
Drug-induced crystal nephropathy: an update.	2008 Mar	18324877
Simultaneous determination of triamterene and hydrochlorothiazide in tablets using derivative spectrophotometry.	2008 May-Jun	18646546
The prince and the pauper. A tale of anticancer targeted agents.	2008 Oct 23	18947424
Determination of diuretics in human urine by hollow fiber-based liquid-liquid-liquid microextraction coupled to high performance liquid chromatography.	2008 Sep	18709193
Responses to diuretic treatment in gene-targeted mice lacking serum- and glucocorticoid-inducible kinase 1.	2009	19401625
Update on the treatment of ocular toxoplasmosis.	2009	19319237
Graz Endocrine Causes of Hypertension (GECOH) study: a diagnostic accuracy study of aldosterone to active renin ratio in screening for primary aldosteronism.	2009 Apr 7	19351411
Consensus guidelines for oral dosing of primarily renally cleared medications in older adults.	2009 Feb	19170784
[Asynchronous lumbar synovial cysts after surgical resection: a case report].	2009 Mar-Apr	19358082
Heritable forms of hypertension.	2009 Oct	17647025

Patents

Sample Use Guides

In Vivo Use Guide

Edema: Oral: 100 to 300 mg daily in 1 to 2 divided doses; maximum dose: 300 mg daily

Route of Administration: Oral

In Vitro Use Guide

Triamterene in the concentration range from 8X10(-13) mol/l to 8X10(-3) mol/l exerted a dose-dependent inhibitory effect of the rat kidney plasma membrane Na-K-Mg-ATPase and Na-K-ATPase activities--estimated IC50 values lay at about 8X10(-3) mol/l and 8X10(-7) mol/l, respectively.

Name

Type

Language

DYAZIDE COMPONENT TRIAMTERENE

Preferred Name

English

TRIAMTERENE

Official Name

English

SK&F 8542

Code

English

TRIAMTERENE [USP MONOGRAPH]

Common Name

English

2,4,7-PTERIDINETRIAMINE, 6-PHENYL-

Systematic Name

English

NSC-639359

Code

English

TRIAMTERENE [ORANGE BOOK]

Common Name

English

TRIAMTERENE [JAN]

Common Name

English

TRIAMTERENE [USAN]

Common Name

English

TRIAMTERENE [IARC]

Common Name

English

TRIAMTERENE [USP IMPURITY]

Common Name

English

TRIAMTERENE [USP-RS]

Common Name

English

TRIAMTERENE [MART.]

Common Name

English

triamterene [INN]

Common Name

English

SK-8542

Code

English

MAXZIDE COMPONENT TRIAMTERENE

Common Name

English

2,4,7-Triamino-6-phenylpteridine

Systematic Name

English

NSC-77625

Code

English

TRIAMTERENE [HSDB]

Common Name

English

SK&F-8542

Code

English

TRIAMTERENE [MI]

Common Name

English

TRIAMTERENE [VANDF]

Common Name

English

TRIAMTERENE [EP MONOGRAPH]

Common Name

English

Triamterene [WHO-DD]

Common Name

English

Classification Tree Code System Code

WHO-ATC

C03DB02