AMILORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C6H8ClN7O
Molecular Weight	229.627
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC(=N)NC(=O)C1=C(N)N=C(N)C(Cl)=N1

InChI

InChIKey=XSDQTOBWRPYKKA-UHFFFAOYSA-N

InChI=1S/C6H8ClN7O/c7-2-4(9)13-3(8)1(12-2)5(15)14-6(10)11/h(H4,8,9,13)(H4,10,11,14,15)

HIDE SMILES / InChI

Molecular Formula	C6H8ClN7O
Molecular Weight	229.627
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.drugbank.ca/drugs/DB00594
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/18-200S024_Midamor_Prntlbl.pdf

Amiloride, an antikaliuretic-diuretic agent, is a pyrazine-carbonyl-guanidine that is unrelated chemically to other known antikaliuretic or diuretic agents. It is an antihypertensive, potassium-sparing diuretic that was first approved for use in 1967 and helps to treat hypertension and congestive heart failure. The drug is often used in conjunction with thiazide or loop diuretics. Due to its potassium-sparing capacities, hyperkalemia (high blood potassium levels) are occasionally observed in patients taking amiloride. Amiloride works by inhibiting sodium reabsorption in the distal convoluted tubules and collecting ducts in the kidneys by binding to the amiloride-sensitive sodium channels. This promotes the loss of sodium and water from the body, but without depleting potassium. It is used for as adjunctive treatment with thiazide diuretics or other kaliuretic-diuretic agents in congestive heart failure or hypertension.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Amiloride-sensitive sodium channel alpha-subunit 5 Target ID: CHEMBL1791 Sources: http://www.drugbank.ca/drugs/DB00594	Inhibitor 8504	776.0 nM [IC50]
Amiloride-sensitive sodium channel subunit beta 3 Target ID: P51168 Gene ID: 6338.0 Gene Symbol: SCNN1B Target Organism: Homo sapiens (Human) Sources: http://www.drugbank.ca/drugs/DB00594	Inhibitor 8504
Amiloride-sensitive sodium channel subunit gamma 3 Target ID: P51170\|\|\|Q96TD2 Gene ID: 6340.0 Gene Symbol: SCNN1G Target Organism: Homo sapiens (Human) Sources: http://www.drugbank.ca/drugs/DB00594	Inhibitor 8504
Amiloride-sensitive cation channel 3 3 Target ID: CHEMBL5368 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19339181	Inhibitor 8504	4.4 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 575 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/18-200S024_Midamor_Prntlbl.pdf	Primary		Approved 8583	Midamor Approved Use Preventing development of low blood potassium or helping to restore normal blood potassium in patients with high blood pressure or heart failure. Launch Date 1981
Heart failure 106 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/18-200S024_Midamor_Prntlbl.pdf	Primary		Approved 8583	Midamor Approved Use Preventing development of low blood potassium or helping to restore normal blood potassium in patients with high blood pressure or heart failure. Launch Date 1981

C_max

Value	Dose	Co-administered	Analyte	Population
20.6 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9085317	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		AMILORIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
1.57 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9085317	17 mmol single, respiratory dose: 17 mmol route of administration: Respiratory experiment type: SINGLE co-administered:		AMILORIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
275 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9085317	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		AMILORIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
16 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9085317	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		AMILORIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
77% DRUG LABEL https://reference.medscape.com/drug/midamor-amiloride-342406#10			AMILORIDE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
25 mg 3 times / day multiple, oral Highest studied dose Dose: 25 mg, 3 times / day Route: oral Route: multiple Dose: 25 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6386025	healthy, 25-44 Health Status: healthy Age Group: 25-44 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/6386025	Sources: https://pubmed.ncbi.nlm.nih.gov/6386025
10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3371085	unhealthy, 58 Health Status: unhealthy Age Group: 58 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/3371085	Disc. AE: Dry mouth, Constipation... AEs leading to discontinuation/dose reduction: Dry mouth (5.5%) Constipation (5.5%) Malaise (moderate, 5.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/3371085
5 mg 3 times / day multiple, oral Recommended Dose: 5 mg, 3 times / day Route: oral Route: multiple Dose: 5 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/5639627	unhealthy Health Status: unhealthy Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/5639627	Disc. AE: Nausea, Weakness... AEs leading to discontinuation/dose reduction: Nausea (severe, 16.7%) Weakness (severe, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/5639627

AEs

AE	Significance	Dose	Population
Constipation	5.5% Disc. AE	10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3371085	unhealthy, 58 Health Status: unhealthy Age Group: 58 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/3371085
Dry mouth	5.5% Disc. AE	10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3371085	unhealthy, 58 Health Status: unhealthy Age Group: 58 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/3371085
Malaise	moderate, 5.5% Disc. AE	10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3371085	unhealthy, 58 Health Status: unhealthy Age Group: 58 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/3371085
Nausea	severe, 16.7% Disc. AE	5 mg 3 times / day multiple, oral Recommended Dose: 5 mg, 3 times / day Route: oral Route: multiple Dose: 5 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/5639627	unhealthy Health Status: unhealthy Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/5639627
Weakness	severe, 16.7% Disc. AE	5 mg 3 times / day multiple, oral Recommended Dose: 5 mg, 3 times / day Route: oral Route: multiple Dose: 5 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/5639627	unhealthy Health Status: unhealthy Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/5639627

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
Cav3.1 7 Cav3.2 12 Cav3.3 7 MATE1 415 MATE2 267 OCT1 620 OAT4 150	MATE1 182 MATE2 98 OCT1 393 OCT2 434

Drug as perpetrator

Target	Modality	Activity
OAT4 150	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17229912/	likely
Cav3.3 7	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22767612/	weak [IC50 1091 uM]
Cav3.1 7	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22767612/	weak [IC50 840 uM]
MATE1 416	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22419765/	yes [IC50 2.41 uM]
MATE2 267	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22419765/	yes [IC50 3.06 uM]
Cav3.2 12	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22767612/	yes [IC50 62 uM]
OCT1 656	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/18788725/	yes

Drug as victim

Target	Modality	Activity
MATE1 182	substrate 4014 Sources: http://www.slib.agu.ac.jp/gakukaisi/pdf/y12_22.pdf	yes
MATE2 98	substrate 4014 Sources: http://www.slib.agu.ac.jp/gakukaisi/pdf/y12_22.pdf	yes
OCT1 393	substrate 4014 Sources: http://www.slib.agu.ac.jp/gakukaisi/pdf/y12_22.pdf	yes
OCT2 434	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/16394027/\|http://www.slib.agu.ac.jp/gakukaisi/pdf/y12_22.pdf	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:2639	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:2639
ChemicalBook	CB7146512	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7146512
eMolecules	1934607	https://www.emolecules.com/cgi-bin/more?vid=1934607
ZINC	ZINC000004340269	http://zinc15.docking.org/substances/ZINC000004340269

PubMed

Title	Date	PubMed
Na(+)-dependent pH regulation by the amitochondriate protozoan parasite Giardia intestinalis.	2001-08-03	11297564
Activation of epithelial sodium channels by prostasin in Xenopus oocytes.	2001-06	11373334
NHE and ICAM-1 expression in hypoxic/reoxygenated coronary microvascular endothelial cells.	2001-06	11356638
cAMP-dependent fluid secretion in rat inner medullary collecting ducts.	2001-06	11352842
Epithelial Na(+) channels are regulated by flow.	2001-06	11352841
Acute adaptive cellular base uptake in rat duodenal epithelium.	2001-06	11352800
Mechanisms of TNF-alpha stimulation of amiloride-sensitive sodium transport across alveolar epithelium.	2001-06	11350806
Bafilomycin A(1) inhibits rhinovirus infection in human airway epithelium: effects on endosome and ICAM-1.	2001-06	11350790
Protease-activated receptor-2-mediated inhibition of ion transport in human bronchial epithelial cells.	2001-06	11350741
A standing Na+ conductance in rat carotid body type I cells.	2001-05-25	11388422
Amiloride-sensitive sodium currents in identified taste cells of the frog.	2001-05-25	11388403
Molecular cloning and characterization of a novel (Na+,K+)/H+ exchanger localized to the trans-Golgi network.	2001-05-18	11279194
Dependence of the acid-sensitive ion channel, ASIC1a, on extracellular Ca(2+) ions.	2001-05-11	11334808
Simultaneous direct determination of amiloride and triamterene in urine using isopotential fluorometry.	2001-05-01	11319818
Lung epithelial ion transport in neonatal lung disease.	2001-05	11359039
Alveolar epithelial barrier functions in ventilated perfused rabbit lungs.	2001-05	11290513
Nongenomic effect of testosterone on chloride secretion in cultured rat efferent duct epithelia.	2001-05	11287329
Roles of the C termini of alpha -, beta -, and gamma -subunits of epithelial Na+ channels (ENaC) in regulating ENaC and mediating its inhibition by cytosolic Na+.	2001-04-27	11278874
Angiotensin II type I receptor modulates intracellular free Mg2+ in renally derived cells via Na+-dependent Ca2+-independent mechanisms.	2001-04-27	11278387
Effect of 2',4'-dichlorobenzamil hydrochloride, a Na(+)-Ca(2+) exchange inhibitor, on human spermatozoa.	2001-04-20	11334878
Oxygen-evoked Na+ transport in rat fetal distal lung epithelial cells.	2001-04-01	11283228
Maxi K+ channels co-localised with CFTR in the apical membrane of an exocrine gland acinus: possible involvement in secretion.	2001-04	11374055
Regulation of Na(+) transport across leech skin by peptide hormones and neurotransmitters.	2001-04	11273812
Effects of SNP, ouabain, and amiloride on electrical potential profile of isolated sheep pleura.	2001-04	11247961
Contribution of amiloride-insensitive pathways to alveolar fluid clearance in adult rats.	2001-04	11247951
Characterization of stretch-activated cation current in coronary smooth muscle cells.	2001-04	11247789
Platelet hyperactivity and abnormal Ca(2+) homeostasis in diabetes mellitus.	2001-04	11247757
Involvement of calcium influx in hypoxia-induced bleb formation in human umbilical vein endothelial cells.	2001-03-27	11267120
Endothelin-1 has a unique oxygen-saving effect by increasing contractile efficiency in the isolated rat heart.	2001-03-20	11257085
[Lithium intoxication due to simultaneous use of trimethoprim].	2001-03-17	11284290
No-flow ischemia inhibits insulin signaling in heart by decreasing intracellular pH.	2001-03-16	11249875
L-arginine effects on Na+ transport in M-1 mouse cortical collecting duct cells--a cationic amino acid absorbing epithelium.	2001-03-15	11318095
Inhibition of Na+-H+ exchanger-3 interferes with apical receptor-mediated endocytosis via vesicle fusion.	2001-03-15	11251045
The essential role of cytosolic Cl- in Ca2+ regulation of an amiloride-sensitive channel in fetal rat pneumocyte.	2001-03-01	11284207
Gramicidin-perforated patch analysis on HCO3- secretion through a forskolin-activated anion channel in rat parotid intralobular duct cells.	2001-03-01	11284200
Effects of SM-20550, a selective Na+-H+ exchange inhibitor, on the ion transport of myocardial mitochondria.	2001-03	11354258
Subtypes of low voltage-activated Ca2+ channels in laterodorsal thalamic neurons: possible localization and physiological roles.	2001-03	11316268
NaCl detection thresholds: comparison of Fischer 344 and Wistar rats.	2001-03	11287385
New quinolone, grepafloxacin, inhibits Cl- secretion across bovine airway epithelium in culture.	2001-03	11264763
The use of a response surface methodology on HPLC analysis of methyldopa, amiloride and hydrochlorothiazide in tablets.	2001-03	11248497
Beta1-adrenergic agonist is a potent stimulator of alveolar fluid clearance in hyperoxic rat lungs.	2001-02	11286398
Oral irritation by sodium chloride: sensitization, self-desensitization, and cross-sensitization to capsaicin.	2001-02	11274673
Na+-dependent recovery of intracellular pH from acid loading in mouse colonic crypt cells.	2001-01	11321046
Isolated working rat heart adaptation after abrupt changes in extracellular Ca2+ concentration.	2001-01	11271512
Inhibition of pig liver and Zea mays L. polyamine oxidase: a comparative study.	2001	11342283
Regulation of tubular cell MCP-1 production by intracellular ions: a role for sodium and calcium.	2001	11340305
Response of alkalinization or acidification by phytohemagglutinin is dependent on the activity of protein kinase C in human peripheral T Cells.	2001	11329615
The myocardial Na+/H+ exchanger: a potential therapeutic target for the prevention of myocardial ischaemic and reperfusion injury and attenuation of postinfarction heart failure.	2001	11293648
Hypertonicity stimulates Cl(-) transport in the intestine of fresh water acclimated eel, Anguilla anguilla.	2001	11275682
Impaired sodium excretion, decreased glomerular filtration rate and elevated blood pressure in endothelin receptor type B deficient rats.	2001	11269510

Patents

Sample Use Guides

In Vivo Use Guide

MIDAMOR (Amiloride), one 5 mg tablet daily, should be added to the usual antihypertensive or diuretic dosage of a kaliuretic diuretic. The dosage may be increased to 10 mg per day, if necessary. More than two 5 mg tablets of MIDAMOR daily usually are not needed, and there is little controlled experience with such doses. If persistent hypokalemia is documented with 10 mg, the dose can be increased to 15 mg, then 20 mg, with careful monitoring of electrolytes. If it is necessary to use MIDAMOR alone (see INDICATIONS), the starting dosage should be one 5 mg tablet daily. This dosage may be increased to 10 mg per day, if necessary. More than two 5 mg tablets usually are not needed, and there is little controlled experience with such doses. If persistent hypokalemia is documented with 10 mg, the dose can be increased to 15 mg, then 20 mg, with careful monitoring of electrolytes.

Route of Administration: Oral

In Vitro Use Guide

Amiloride (10, 30, and 100 μmol/L) concentration-dependently potentiated erlotinib-induced inhibition of cell proliferation and colony formation in the 4 human pancreatic cancer cell lines.

Substance Class	Chemical Created by `admin` on `Wed Apr 02 09:26:13 GMT 2025` Edited by `admin` on `Wed Apr 02 09:26:13 GMT 2025`
Record UNII	7DZO8EB0Z3
Record Status	`Validated (UNII)`
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Name

Type

Language

AMILORIDE

Official Name

English

AMICLARAN

Preferred Name

English

AMILORIDE [MI]

Common Name

English

Amiloride [WHO-DD]

Common Name

English

N-AMIDINO-3,5-DIAMINO-6-CHLOROPYRAZINECARBOXAMIDE

Systematic Name

English

amiloride [INN]

Common Name

English

AMILORIDE [VANDF]

Common Name

English

PYRAZINECARBOXAMIDE, 3,5-DIAMINO-N-(AMINOIMINOMETHYL)-6-CHLORO-

Systematic Name

English

Classification Tree Code System Code

NDF-RT

N0000008859