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 8297		5.0 µM [IC50]
Heart phosphodiesterase 2 Target ID: CHEMBL2111408 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6321204	Inhibitor 8297		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 8429	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
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 1054 BCRP 561

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
BCRP 561	substrate 3367 Sources: https://dmd.aspetjournals.org/content/36/6/995 Page: 3.0	yes
CYP1A2 1054	substrate 3367 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
Folic acid antagonists during pregnancy and risk of birth defects.	2001 Mar 22	11263425
Neural tube defects in relation to use of folic acid antagonists during pregnancy.	2001 May 15	11384952
In vitro antioxidant and photo-oxidant properties of dipyridamole.	2001 Nov-Dec	11797818
Prolonged exercise following diuretic-induced hypohydration effects on fluid and electrolyte hormones.	2001 Sep	11561214
Determination of hydrochlorothiazide, triamterene and propranolol hydrochloride by the spectrophotometric method and high-performance liquid chromatography (HPLC).	2001 Sep-Oct	11876440
Effects of anion and cation inhibitors and carbonic anhydrase inhibitors upon the activity of the gypsy moth (Lepidoptera: Lymantriidae) nucleo-polyhedrovirus.	2002 Apr	12019995
Use of the trispan device to assist coil embolization of high-flow arteriovenous fistulas.	2002 Aug	12169472
Screening for 18 diuretics and probenecid in doping analysis by liquid chromatography-tandem mass spectrometry.	2002 Dec	12474217
Non-traumatic neurological emergencies: emergency neuroradiological interventions.	2002 Jul	12111055
[Liddle's syndrome: late diagnosis of a rare cause of arterial hypertension].	2002 May-Jun	14647783
Direct determination of triamterene by potentiometry using a coated wire selective electrode.	2003 Dec 4	14656588
Drug-induced myopia.	2003 Feb	12602401
Pharmacological characterization of unique prazosin-binding sites in human kidney.	2003 Jul	12827214
Photostability studies on the furosemide-triamterene drug association.	2003 Sep	13679181
Treatment of congenital nephrogenic diabetes insipidus with hydrochlorothiazide and amiloride in an adult patient.	2004	14646392
[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
Application of a fluorescence sensor for miniscale on-line monitoring of powder mixing kinetics.	2004 Jan	14648636
[Circadian rhythm of the renin-angiotensin-aldosterone system: a summary of our research studies].	2004 Jul-Aug	15553256
Triamterene-beta-cyclodextrin systems: preparation, characterization and in vivo evaluation.	2004 Mar 29	15198540
Attenuation of the kaluretic properties of furosemide by triamterene (Dyrenium) in healthy volunteers.	2005 Feb	15726878
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Hydrochlorothiazide-induced noncardiogenic pulmonary edema: an underrecognized yet serious adverse drug reaction.	2005 Sep	16164399
[Drug-induced renal calculi].	2006 Apr	16709005
[Liddle syndrome: Pathogenesis, pathophysiology, and therapy].	2006 Feb	16523945
Periprocedural morbidity and mortality by endovascular treatment of cerebral aneurysms with GDC: a retrospective 12-year experience of a single center.	2007 Apr	17216530
Naturalised Vitis rootstocks in Europe and consequences to native wild grapevine.	2007 Jun 13	17565374
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
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
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
Responses to diuretic treatment in gene-targeted mice lacking serum- and glucocorticoid-inducible kinase 1.	2009	19401625
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

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

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 [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 COMPONENT OF MAXZIDE

Common Name

English

TRIAMTERENE [EP MONOGRAPH]

Common Name

English

Triamterene [WHO-DD]

Common Name

English

Classification Tree Code System Code

WHO-ATC

C03DB02