TRIAMTERENE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C12H11N7
Molecular Weight	253.2631
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

c1ccc(cc1)-c2c(=N)nc3-c(c(N)[nH]c(=N)[nH]3)n2

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 7728		5.0 µM [IC50]
Heart phosphodiesterase 2 Target ID: CHEMBL2111408 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6321204	Inhibitor 7728		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 8043	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 -1.70294395E11

C_max

Value	Dose	Co-administered	Analyte	Population
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
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
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

AUC

Value	Dose	Co-administered	Analyte	Population
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
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
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

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
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
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

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 Co-administed with:: hydrochlorothiazide(50 mg twice daily; 28 days) Sources: https://pubmed.ncbi.nlm.nih.gov/6496322	unhealthy, 54 ± 3 years n = 9 Health Status: unhealthy Condition: hypokalemia Age Group: 54 ± 3 years Population Size: 9 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 Co-administed with:: hydrochlorothiazide(25 mg) 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 Co-administed with:: hydrochlorothiazide(50 mg twice daily; 28 days) Sources: https://pubmed.ncbi.nlm.nih.gov/6496322	unhealthy, 54 ± 3 years n = 9 Health Status: unhealthy Condition: hypokalemia Age Group: 54 ± 3 years Population Size: 9 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 Co-administed with:: hydrochlorothiazide(25 mg) 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 972 BCRP 515

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
BCRP 515	substrate 3113 Sources: https://dmd.aspetjournals.org/content/36/6/995 Page: 3.0	yes
CYP1A2 972	substrate 3113 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
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
eMolecules	594844	https://www.emolecules.com/cgi-bin/more?vid=594844

PubMed

Title	Date	PubMed
Irreversible renal failure associated with triamterene.	1991	1819215
Micellar electrokinetic capillary chromatography analysis of diuretics in pharmaceutical formulations.	2002 May 16	18968622
Drug-induced urinary calculi.	2003 Fall	16985842
[Determination of five components in compound hypotensive tablet by HPLC].	2004 Aug	15563064
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
The G-tolerance after pharmacological hypohydration.	2004 Jul	16231450
[Circadian rhythm of the renin-angiotensin-aldosterone system: a summary of our research studies].	2004 Jul-Aug	15553256
Use of the TriSpan coil to facilitate the transcatheter occlusion of pulmonary arteriovenous malformation.	2004 Nov-Dec	15593430
Differing effects of mineralocorticoid receptor-dependent and -independent potassium-sparing diuretics on fibrinolytic balance.	2005 Aug	15998706
[Capillary electrophoresis with end-column electrochemical detection for hydrochlorothiazide and triamterene diuretics].	2005 Jan	15881361
[A case of Gitelman's syndrome presenting with severe hypocalcaemia and hypokalemic periodic paralysis].	2005 Jul	16078592
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
Multicommuted flow-through fluorescence optosensor for determination of furosemide and triamterene.	2005 Nov	16211379
Drug-induced megaloblastic anemia.	2005 Oct	16187172
[Differential diagnosis of a macrocytic, hyperchromic anemia following alcohol abuse and simultaneous therapy with triamterene and cotrimoxazole].	2005 Sep 23	16172954
Design, synthesis and diuretic activity of some novel 2,4-diamino-6-aryl-7-arylaminopyrimido [4,5-d]pyrimidin-5(6H)-ones.	2006	16889118
[Drug-induced renal calculi].	2006 Apr	16709005
High-speed gas chromatography in doping control: fast-GC and fast-GC/MS determination of beta-adrenoceptor ligands and diuretics.	2006 Dec	17305237
Fast gas chromatographic/mass spectrometric determination of diuretics and masking agents in human urine: Development and validation of a productive screening protocol for antidoping analysis.	2006 Dec 1	17027009
[Liddle syndrome: Pathogenesis, pathophysiology, and therapy].	2006 Feb	16523945
[Diuretic therapy in heart failure].	2006 Jan-Feb	16634001
Potassium-sparing diuretics.	2006 Jul 11-17	16869220
[Influence of diuretics on occupationally important qualities of engine drivers].	2007	17354601
Early onset pauciarticular arthritis is the major risk factor for naproxen-induced pseudoporphyria in juvenile idiopathic arthritis.	2007	17266758
Periprocedural morbidity and mortality by endovascular treatment of cerebral aneurysms with GDC: a retrospective 12-year experience of a single center.	2007 Apr	17216530
Stereoselective syntheses of the 2-Isopropenyl-2,3-dihydrobenzofuran nucleus: potential chiral building blocks for the syntheses of tremetone, hydroxytremetone, and rotenone.	2007 Apr 13	17375958
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

TRIAMTERENE

Official Name

English

DYAZIDE COMPONENT TRIAMTERENE

Common Name

English

SK&F 8542

Code

English

TRIAMTERENE [USP MONOGRAPH]

Common Name

English

TRIAMTERENE [WHO-DD]

Common Name

English

TRIAMTERENE [USP]

Common Name

English

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

Systematic Name

English

TRIAMTERENE COMPONENT OF DYAZIDE

Common Name

English

NSC-639359

Code

English

TRIAMTERENE [ORANGE BOOK]

Common Name

English

TRIAMTERENE [USAN]

Common Name

English

TRIAMTERENE [IARC]

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 COMPONENT OF MAXZIDE

Common Name

English

TRIAMTERENE [EP MONOGRAPH]

Common Name

English

Classification Tree Code System Code

WHO-ATC

C03DB02