AMILORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C6H8ClN7O
Molecular Weight	229.627
Optical Activity	UNSPECIFIED
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

Description

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	Condition	Potency
Amiloride-sensitive cation channel 3 3	Inhibitor 7464		4.4 µM [IC50]
Amiloride-sensitive sodium channel subunit gamma 3	Inhibitor 7464	Hypertension
Amiloride-sensitive sodium channel alpha-subunit 5	Inhibitor 7464	Hypertension	776.0 nM [IC50]
Amiloride-sensitive sodium channel subunit beta 3	Inhibitor 7464	Hypertension

Conditions

Condition	Modality	Targets	Highest Phase	Product
Heart Failure 148	Primary	Amiloride-sensitive sodium channel alpha-subunit Amiloride-sensitive sodium channel subunit beta Amiloride-sensitive sodium channel subunit gamma	Approved 7888	Midamor
Hypertension 563	Primary	Amiloride-sensitive sodium channel alpha-subunit Amiloride-sensitive sodium channel subunit beta Amiloride-sensitive sodium channel subunit gamma	Approved 7888	Midamor
[Cystic fibrosis, Li-induced polyuria] 3			Approved (off-label) 8

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
Regulation of Na(+) transport across leech skin by peptide hormones and neurotransmitters.	2001 Apr	11273812
Contribution of amiloride-insensitive pathways to alveolar fluid clearance in adult rats.	2001 Apr	11247951
Angiotensin II type I receptor modulates intracellular free Mg2+ in renally derived cells via Na+-dependent Ca2+-independent mechanisms.	2001 Apr 27	11278387
Beta1-adrenergic agonist is a potent stimulator of alveolar fluid clearance in hyperoxic rat lungs.	2001 Feb	11286398
Oral irritation by sodium chloride: sensitization, self-desensitization, and cross-sensitization to capsaicin.	2001 Feb	11274673
Location and function of the epithelial Na channel in the cochlea.	2001 Feb	11208596
Resorptive state and cell size influence intracellular pH regulation in rabbit osteoclasts cultured on collagen-hydroxyapatite films.	2001 Feb	11182377
Mechanisms of iron transport into rat erythroid cells.	2001 Feb	11169456
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
Na(+)-dependent fluid absorption in intact perfused rat colonic crypts.	2001 Jan	11208723
Transport of [3H]MPP+ in an immortalized rat brain microvessel endothelial cell line (RBE 4).	2001 Jan	11191826
Magnesium transport in the renal distal convoluted tubule.	2001 Jan	11152754
Functional role of sodium-calcium exchange in the regulation of renal vascular resistance.	2001 Jan	11133525
Differential transduction mechanisms underlying NaCl- and KCl-induced responses in mouse taste cells.	2001 Jan	11124217
Activation of epithelial sodium channels by prostasin in Xenopus oocytes.	2001 Jun	11373334
Epithelial Na(+) channels are regulated by flow.	2001 Jun	11352841
NaCl detection thresholds: comparison of Fischer 344 and Wistar rats.	2001 Mar	11287385
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
The distal convoluted tubule of rabbit kidney does not express a functional sodium channel.	2001 Mar	11181416
Expression and regulation of normal and polymorphic epithelial sodium channel by human lymphocytes.	2001 Mar 16	11113130
Lung epithelial ion transport in neonatal lung disease.	2001 May	11359039
Dependence of the acid-sensitive ion channel, ASIC1a, on extracellular Ca(2+) ions.	2001 May 11	11334808

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.

Name

Type

Language

AMILORIDE

Official Name

English

AMILORIDE [WHO-DD]

Common Name

English

AMILORIDE [MI]

Common Name

English

AMICLARAN

Brand 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