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 8297	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 8297
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 8297
Amiloride-sensitive cation channel 3 3 Target ID: CHEMBL5368 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19339181	Inhibitor 8297	4.4 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 567 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/18-200S024_Midamor_Prntlbl.pdf	Primary		Approved 8429	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 103 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/18-200S024_Midamor_Prntlbl.pdf	Primary		Approved 8429	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 Page: p.372	healthy, 25-44 n = 5 Health Status: healthy Age Group: 25-44 Sex: M Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/6386025 Page: p.372	Sources: https://pubmed.ncbi.nlm.nih.gov/6386025 Page: p.372
10 mg 1 times / day multiple, oral (max) Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Co-administed with:: furosemide, p.o(40 mg; q.d) Sources: https://pubmed.ncbi.nlm.nih.gov/3371085 Page: p.696	unhealthy, 58 n = 18 Health Status: unhealthy Condition: Hypertension Age Group: 58 Sex: M+F Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/3371085 Page: p.696	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 Page: p.696
5 mg 3 times / day multiple, oral Recommended Dose: 5 mg, 3 times / day Route: oral Route: multiple Dose: 5 mg, 3 times / day Co-administed with:: hydrochlorothiazide, p.o(50 mg; q.d) Sources: https://pubmed.ncbi.nlm.nih.gov/5639627 Page: p.423	unhealthy n = 12 Health Status: unhealthy Condition: Hypertension Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/5639627 Page: p.423	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 Page: p.423

AEs

AE	Significance	Dose	Population
Constipation	5.5% Disc. AE	10 mg 1 times / day multiple, oral (max) Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Co-administed with:: furosemide, p.o(40 mg; q.d) Sources: https://pubmed.ncbi.nlm.nih.gov/3371085 Page: p.696	unhealthy, 58 n = 18 Health Status: unhealthy Condition: Hypertension Age Group: 58 Sex: M+F Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/3371085 Page: p.696
Dry mouth	5.5% Disc. AE	10 mg 1 times / day multiple, oral (max) Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Co-administed with:: furosemide, p.o(40 mg; q.d) Sources: https://pubmed.ncbi.nlm.nih.gov/3371085 Page: p.696	unhealthy, 58 n = 18 Health Status: unhealthy Condition: Hypertension Age Group: 58 Sex: M+F Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/3371085 Page: p.696
Malaise	moderate, 5.5% Disc. AE	10 mg 1 times / day multiple, oral (max) Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Co-administed with:: furosemide, p.o(40 mg; q.d) Sources: https://pubmed.ncbi.nlm.nih.gov/3371085 Page: p.696	unhealthy, 58 n = 18 Health Status: unhealthy Condition: Hypertension Age Group: 58 Sex: M+F Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/3371085 Page: p.696
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 Co-administed with:: hydrochlorothiazide, p.o(50 mg; q.d) Sources: https://pubmed.ncbi.nlm.nih.gov/5639627 Page: p.423	unhealthy n = 12 Health Status: unhealthy Condition: Hypertension Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/5639627 Page: p.423
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 Co-administed with:: hydrochlorothiazide, p.o(50 mg; q.d) Sources: https://pubmed.ncbi.nlm.nih.gov/5639627 Page: p.423	unhealthy n = 12 Health Status: unhealthy Condition: Hypertension Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/5639627 Page: p.423

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
Cav3.1 7 Cav3.2 12 Cav3.3 7 MATE1 306 MATE2 263 OCT1 512 OAT4 146	MATE1 135 MATE2 96 OCT1 327 OCT2 355

Drug as perpetrator

Target	Modality	Activity
OAT4 146	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17229912/	likely
Cav3.3 7	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22767612/	weak [IC50 1091 uM]
Cav3.1 7	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22767612/	weak [IC50 840 uM]
MATE1 308	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22419765/	yes [IC50 2.41 uM]
MATE2 263	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22419765/	yes [IC50 3.06 uM]
Cav3.2 12	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22767612/	yes [IC50 62 uM]
OCT1 543	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/18788725/	yes

Drug as victim

Target	Modality	Activity
MATE1 135	substrate 3367 Sources: http://www.slib.agu.ac.jp/gakukaisi/pdf/y12_22.pdf	yes
MATE2 96	substrate 3367 Sources: http://www.slib.agu.ac.jp/gakukaisi/pdf/y12_22.pdf	yes
OCT1 327	substrate 3367 Sources: http://www.slib.agu.ac.jp/gakukaisi/pdf/y12_22.pdf	yes
OCT2 355	substrate 3367 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
ZINC	ZINC000004340269	http://zinc15.docking.org/substances/ZINC000004340269
eMolecules	1934607	https://www.emolecules.com/cgi-bin/more?vid=1934607

PubMed

Title	Date	PubMed
Acute effects of lithium on the renal concentrating mechanism in a primate.	1975 Mar	1115255
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
Maxi K+ channels co-localised with CFTR in the apical membrane of an exocrine gland acinus: possible involvement in secretion.	2001 Apr	11374055
Effects of SNP, ouabain, and amiloride on electrical potential profile of isolated sheep pleura.	2001 Apr	11247961
Contribution of amiloride-insensitive pathways to alveolar fluid clearance in adult rats.	2001 Apr	11247951
Na(+)-dependent pH regulation by the amitochondriate protozoan parasite Giardia intestinalis.	2001 Aug 3	11297564
Resorptive state and cell size influence intracellular pH regulation in rabbit osteoclasts cultured on collagen-hydroxyapatite films.	2001 Feb	11182377
The binding-site crevice of the D4 dopamine receptor is coupled to three distinct sites of allosteric modulation.	2001 Feb	11160618
Pontine gustatory activity is altered by electrical stimulation in the central nucleus of the amygdala.	2001 Feb	11160511
Inhibition of the NA(+)/H(+) exchanger reduces rat hepatic stellate cell activity and liver fibrosis: an in vitro and in vivo study.	2001 Feb	11159895
Expression of multiple Na+/H+ exchanger isoforms in cultured epithelial cells from rat efferent duct and cauda epididymidis.	2001 Feb	11159350
Ion exchange activity in pulmonary artery smooth muscle cells: the response to hypoxia.	2001 Feb	11159005
The transient receptor potential protein homologue TRP6 is the essential component of vascular alpha(1)-adrenoceptor-activated Ca(2+)-permeable cation channel.	2001 Feb 16	11179201
The cytoplasmic C-terminal fragment of polycystin-1 regulates a Ca2+-permeable cation channel.	2001 Feb 9	11044446
Na+/H+ antiporter from Synechocystis species PCC 6803, homologous to SOS1, contains an aspartic residue and long C-terminal tail important for the carrier activity.	2001 Jan	11154351
Functional role of sodium-calcium exchange in the regulation of renal vascular resistance.	2001 Jan	11133525
Activation of epithelial sodium channels by prostasin in Xenopus oocytes.	2001 Jun	11373334
Acute adaptive cellular base uptake in rat duodenal epithelium.	2001 Jun	11352800
Subtypes of low voltage-activated Ca2+ channels in laterodorsal thalamic neurons: possible localization and physiological roles.	2001 Mar	11316268
NaCl detection thresholds: comparison of Fischer 344 and Wistar rats.	2001 Mar	11287385
The use of a response surface methodology on HPLC analysis of methyldopa, amiloride and hydrochlorothiazide in tablets.	2001 Mar	11248497
Complexities of measuring antagonist potency at P2X(7) receptor orthologs.	2001 Mar	11181928
Collecting duct is a site of sodium retention in PAN nephrosis: a rationale for amiloride therapy.	2001 Mar	11181809
Catecholamines increase lung edema clearance in rats with increased left atrial pressure.	2001 Mar	11181624
Inhibition of Na+-H+ exchanger-3 interferes with apical receptor-mediated endocytosis via vesicle fusion.	2001 Mar 15	11251045
No-flow ischemia inhibits insulin signaling in heart by decreasing intracellular pH.	2001 Mar 16	11249875
Endothelin-1 has a unique oxygen-saving effect by increasing contractile efficiency in the isolated rat heart.	2001 Mar 20	11257085
Lung epithelial ion transport in neonatal lung disease.	2001 May	11359039
Alveolar epithelial barrier functions in ventilated perfused rabbit lungs.	2001 May	11290513
A standing Na+ conductance in rat carotid body type I cells.	2001 May 25	11388422
Amiloride-sensitive sodium currents in identified taste cells of the frog.	2001 May 25	11388403

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 `Sat Dec 16 17:40:55 GMT 2023` Edited by `admin` on `Sat Dec 16 17:40:55 GMT 2023`
Record UNII	7DZO8EB0Z3
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AMILORIDE

Official Name

English

AMILORIDE [MI]

Common Name

English

AMICLARAN

Brand 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