U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C6H8ClN7O.ClH.2H2O
Molecular Weight 302.119
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AMILORIDE HYDROCHLORIDE

SMILES

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

InChI

InChIKey=LTKVFMLMEYCWMK-UHFFFAOYSA-N
InChI=1S/C6H8ClN7O.ClH.2H2O/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);1H;2*1H2

HIDE SMILES / InChI

Description
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

Curator's Comment: Amiloride can cross the blood–brain barrier and has proven beneficial in the treatment of several neuropathological conditions including brain ischemia

Originator

Curator's Comment: Amiloride was discovered in the late 1960s during an extensive screening process at the Merck Sharp and Dohme Research Laboratories # Merck Sharp and Dohme Research Laboratories

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
776.0 nM [IC50]
Target ID: P51168
Gene ID: 6338.0
Gene Symbol: SCNN1B
Target Organism: Homo sapiens (Human)
Target ID: P51170|||Q96TD2
Gene ID: 6340.0
Gene Symbol: SCNN1G
Target Organism: Homo sapiens (Human)
4.4 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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
Primary
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
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
20.6 ng/mL
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
275 ng × h/mL
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
16 h
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
77%
AMILORIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse 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: Page: p.372
healthy, 25-44
n = 5
Health Status: healthy
Age Group: 25-44
Sex: M
Population Size: 5
Sources: 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: Page: p.696
unhealthy, 58
n = 18
Health Status: unhealthy
Condition: Hypertension
Age Group: 58
Sex: M+F
Population Size: 18
Sources: 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: 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: Page: p.423
unhealthy
n = 12
Health Status: unhealthy
Condition: Hypertension
Sex: M+F
Population Size: 12
Sources: Page: p.423
Disc. AE: Nausea, Weakness...
AEs leading to
discontinuation/dose reduction:
Nausea (severe, 16.7%)
Weakness (severe, 16.7%)
Sources: Page: p.423
AEs

AEs

AESignificanceDosePopulation
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: Page: p.696
unhealthy, 58
n = 18
Health Status: unhealthy
Condition: Hypertension
Age Group: 58
Sex: M+F
Population Size: 18
Sources: 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: Page: p.696
unhealthy, 58
n = 18
Health Status: unhealthy
Condition: Hypertension
Age Group: 58
Sex: M+F
Population Size: 18
Sources: 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: Page: p.696
unhealthy, 58
n = 18
Health Status: unhealthy
Condition: Hypertension
Age Group: 58
Sex: M+F
Population Size: 18
Sources: 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: Page: p.423
unhealthy
n = 12
Health Status: unhealthy
Condition: Hypertension
Sex: M+F
Population Size: 12
Sources: 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: Page: p.423
unhealthy
n = 12
Health Status: unhealthy
Condition: Hypertension
Sex: M+F
Population Size: 12
Sources: Page: p.423
PubMed

PubMed

TitleDatePubMed
Inhibition of pig liver and Zea mays L. polyamine oxidase: a comparative study.
2001
Regulation of tubular cell MCP-1 production by intracellular ions: a role for sodium and calcium.
2001
Response of alkalinization or acidification by phytohemagglutinin is dependent on the activity of protein kinase C in human peripheral T Cells.
2001
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
Hypertonicity stimulates Cl(-) transport in the intestine of fresh water acclimated eel, Anguilla anguilla.
2001
Impaired sodium excretion, decreased glomerular filtration rate and elevated blood pressure in endothelin receptor type B deficient rats.
2001
Maxi K+ channels co-localised with CFTR in the apical membrane of an exocrine gland acinus: possible involvement in secretion.
2001 Apr
Regulation of Na(+) transport across leech skin by peptide hormones and neurotransmitters.
2001 Apr
Effects of SNP, ouabain, and amiloride on electrical potential profile of isolated sheep pleura.
2001 Apr
Contribution of amiloride-insensitive pathways to alveolar fluid clearance in adult rats.
2001 Apr
Characterization of stretch-activated cation current in coronary smooth muscle cells.
2001 Apr
Platelet hyperactivity and abnormal Ca(2+) homeostasis in diabetes mellitus.
2001 Apr
Oxygen-evoked Na+ transport in rat fetal distal lung epithelial cells.
2001 Apr 1
Effect of 2',4'-dichlorobenzamil hydrochloride, a Na(+)-Ca(2+) exchange inhibitor, on human spermatozoa.
2001 Apr 20
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 Apr 27
Angiotensin II type I receptor modulates intracellular free Mg2+ in renally derived cells via Na+-dependent Ca2+-independent mechanisms.
2001 Apr 27
Na(+)-dependent pH regulation by the amitochondriate protozoan parasite Giardia intestinalis.
2001 Aug 3
Beta1-adrenergic agonist is a potent stimulator of alveolar fluid clearance in hyperoxic rat lungs.
2001 Feb
Oral irritation by sodium chloride: sensitization, self-desensitization, and cross-sensitization to capsaicin.
2001 Feb
Involvement of calcium influx in hypoxia-induced bleb formation in human umbilical vein endothelial cells.
2001 Feb-Mar
Na+-dependent recovery of intracellular pH from acid loading in mouse colonic crypt cells.
2001 Jan
Isolated working rat heart adaptation after abrupt changes in extracellular Ca2+ concentration.
2001 Jan
Activation of epithelial sodium channels by prostasin in Xenopus oocytes.
2001 Jun
NHE and ICAM-1 expression in hypoxic/reoxygenated coronary microvascular endothelial cells.
2001 Jun
cAMP-dependent fluid secretion in rat inner medullary collecting ducts.
2001 Jun
Epithelial Na(+) channels are regulated by flow.
2001 Jun
Acute adaptive cellular base uptake in rat duodenal epithelium.
2001 Jun
Mechanisms of TNF-alpha stimulation of amiloride-sensitive sodium transport across alveolar epithelium.
2001 Jun
Bafilomycin A(1) inhibits rhinovirus infection in human airway epithelium: effects on endosome and ICAM-1.
2001 Jun
Protease-activated receptor-2-mediated inhibition of ion transport in human bronchial epithelial cells.
2001 Jun
Effects of SM-20550, a selective Na+-H+ exchange inhibitor, on the ion transport of myocardial mitochondria.
2001 Mar
Subtypes of low voltage-activated Ca2+ channels in laterodorsal thalamic neurons: possible localization and physiological roles.
2001 Mar
NaCl detection thresholds: comparison of Fischer 344 and Wistar rats.
2001 Mar
New quinolone, grepafloxacin, inhibits Cl- secretion across bovine airway epithelium in culture.
2001 Mar
The use of a response surface methodology on HPLC analysis of methyldopa, amiloride and hydrochlorothiazide in tablets.
2001 Mar
The essential role of cytosolic Cl- in Ca2+ regulation of an amiloride-sensitive channel in fetal rat pneumocyte.
2001 Mar 1
Gramicidin-perforated patch analysis on HCO3- secretion through a forskolin-activated anion channel in rat parotid intralobular duct cells.
2001 Mar 1
L-arginine effects on Na+ transport in M-1 mouse cortical collecting duct cells--a cationic amino acid absorbing epithelium.
2001 Mar 15
Inhibition of Na+-H+ exchanger-3 interferes with apical receptor-mediated endocytosis via vesicle fusion.
2001 Mar 15
No-flow ischemia inhibits insulin signaling in heart by decreasing intracellular pH.
2001 Mar 16
[Lithium intoxication due to simultaneous use of trimethoprim].
2001 Mar 17
Endothelin-1 has a unique oxygen-saving effect by increasing contractile efficiency in the isolated rat heart.
2001 Mar 20
Lung epithelial ion transport in neonatal lung disease.
2001 May
Alveolar epithelial barrier functions in ventilated perfused rabbit lungs.
2001 May
Nongenomic effect of testosterone on chloride secretion in cultured rat efferent duct epithelia.
2001 May
Simultaneous direct determination of amiloride and triamterene in urine using isopotential fluorometry.
2001 May 1
Dependence of the acid-sensitive ion channel, ASIC1a, on extracellular Ca(2+) ions.
2001 May 11
Molecular cloning and characterization of a novel (Na+,K+)/H+ exchanger localized to the trans-Golgi network.
2001 May 18
A standing Na+ conductance in rat carotid body type I cells.
2001 May 25
Amiloride-sensitive sodium currents in identified taste cells of the frog.
2001 May 25
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
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.
Name Type Language
AMILORIDE HYDROCHLORIDE
EP   MART.   ORANGE BOOK   USAN   USP   USP-RS   VANDF  
USAN  
Official Name English
NSC-755847
Code English
AMILORIDE HYDROCHLORIDE COMPONENT OF MODURETIC
Common Name English
AMILORIDE HYDROCHLORIDE DIHYDRATE [MI]
Common Name English
AMILORIDE HYDROCHLORIDE [USP MONOGRAPH]
Common Name English
AMILORIDE HYDROCHLORIDE [USP-RS]
Common Name English
AMILORIDE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
AMILORIDE HYDROCHLORIDE [EP IMPURITY]
Common Name English
Amiloride hydrochloride dihydrate [WHO-DD]
Common Name English
AMILORIDE HCL
Common Name English
AMILORIDE HYDROCHLORIDE [USAN]
Common Name English
AMILORIDE HYDROCHLORIDE COMPONENT OF HYDRO-RIDE
Common Name English
MODURETIC COMPONENT AMILORIDE HYDROCHLORIDE
Common Name English
AMILORIDE HYDROCHLORIDE [VANDF]
Common Name English
PYRAZINECARBOXAMIDE, 3,5-DIAMINO-N-(AMINOIMINOMETHYL)-6-CHLORO-, MONOHYDROCHLORIDE DIHYDRATE
Common Name English
N-Amidino-3,5-diamino-6-chloropyrazinecarboxamide monohydrochloride dihydrate
Systematic Name English
AMILORIDE HYDROCHLORIDE [MART.]
Common Name English
AMILORIDE HYDROCHLORIDE DIHYDRATE
MI   WHO-DD  
Common Name English
AMILORIDE HYDROCHLORIDE DEHYDRATE [WHO-IP]
Common Name English
AMILORIDE HYDROCHLORIDE DIHYDRATE [EP MONOGRAPH]
Common Name English
MIDAMOR
Brand Name English
HYDRO-RIDE COMPONENT AMILORIDE HYDROCHLORIDE
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C49186
Created by admin on Fri Dec 15 17:23:05 GMT 2023 , Edited by admin on Fri Dec 15 17:23:05 GMT 2023
FDA ORPHAN DRUG 48190
Created by admin on Fri Dec 15 17:23:05 GMT 2023 , Edited by admin on Fri Dec 15 17:23:05 GMT 2023
EU-Orphan Drug EU/3/03/147
Created by admin on Fri Dec 15 17:23:05 GMT 2023 , Edited by admin on Fri Dec 15 17:23:05 GMT 2023
NCI_THESAURUS C582
Created by admin on Fri Dec 15 17:23:06 GMT 2023 , Edited by admin on Fri Dec 15 17:23:06 GMT 2023
Code System Code Type Description
PUBCHEM
68540
Created by admin on Fri Dec 15 17:23:06 GMT 2023 , Edited by admin on Fri Dec 15 17:23:06 GMT 2023
PRIMARY
ChEMBL
CHEMBL945
Created by admin on Fri Dec 15 17:23:05 GMT 2023 , Edited by admin on Fri Dec 15 17:23:05 GMT 2023
PRIMARY
RXCUI
142424
Created by admin on Fri Dec 15 17:23:06 GMT 2023 , Edited by admin on Fri Dec 15 17:23:06 GMT 2023
PRIMARY RxNorm
CHEBI
84743
Created by admin on Fri Dec 15 17:23:05 GMT 2023 , Edited by admin on Fri Dec 15 17:23:05 GMT 2023
PRIMARY
NSC
755847
Created by admin on Fri Dec 15 17:23:06 GMT 2023 , Edited by admin on Fri Dec 15 17:23:06 GMT 2023
PRIMARY
MERCK INDEX
m1671
Created by admin on Fri Dec 15 17:23:05 GMT 2023 , Edited by admin on Fri Dec 15 17:23:05 GMT 2023
PRIMARY Merck Index
WHO INTERNATIONAL PHARMACOPEIA
AMILORIDE HYDROCHLORIDE
Created by admin on Fri Dec 15 17:23:06 GMT 2023 , Edited by admin on Fri Dec 15 17:23:06 GMT 2023
PRIMARY Description: A pale yellow to greenish yellow powder; odourless or almost odourless. Solubility: Slightly soluble in water and ethanol (~750 g/l) TS; practically insoluble in ether R. Category: Diuretic. Storage: Amiloride hydrochloride should be kept in a well-closed container, protected from light. Definition: Amiloride hydrochloride contains not less than 98.0% and not more than 101.0% of C6H8ClN7O,HCl, calculated with reference to the dried substance.
EVMPD
SUB00445MIG
Created by admin on Fri Dec 15 17:23:05 GMT 2023 , Edited by admin on Fri Dec 15 17:23:05 GMT 2023
PRIMARY
FDA UNII
FZJ37245UC
Created by admin on Fri Dec 15 17:23:05 GMT 2023 , Edited by admin on Fri Dec 15 17:23:05 GMT 2023
PRIMARY
DAILYMED
FZJ37245UC
Created by admin on Fri Dec 15 17:23:05 GMT 2023 , Edited by admin on Fri Dec 15 17:23:05 GMT 2023
PRIMARY
EVMPD
SUB21895
Created by admin on Fri Dec 15 17:23:05 GMT 2023 , Edited by admin on Fri Dec 15 17:23:05 GMT 2023
PRIMARY
SMS_ID
100000088483
Created by admin on Fri Dec 15 17:23:06 GMT 2023 , Edited by admin on Fri Dec 15 17:23:06 GMT 2023
PRIMARY
EPA CompTox
DTXSID80169826
Created by admin on Fri Dec 15 17:23:05 GMT 2023 , Edited by admin on Fri Dec 15 17:23:05 GMT 2023
PRIMARY
RS_ITEM_NUM
1019701
Created by admin on Fri Dec 15 17:23:06 GMT 2023 , Edited by admin on Fri Dec 15 17:23:06 GMT 2023
PRIMARY
DRUG BANK
DBSALT001807
Created by admin on Fri Dec 15 17:23:05 GMT 2023 , Edited by admin on Fri Dec 15 17:23:05 GMT 2023
PRIMARY
CAS
17440-83-4
Created by admin on Fri Dec 15 17:23:05 GMT 2023 , Edited by admin on Fri Dec 15 17:23:05 GMT 2023
PRIMARY
NCI_THESAURUS
C47390
Created by admin on Fri Dec 15 17:23:05 GMT 2023 , Edited by admin on Fri Dec 15 17:23:05 GMT 2023
PRIMARY