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
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
DescriptionSources: http://www.drugbank.ca/drugs/DB00594Curator's Comment: Description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/18-200S024_Midamor_Prntlbl.pdf
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21534729
Curator's Comment: Amiloride can cross the blood–brain barrier and has proven beneficial in the treatment of several neuropathological conditions including brain ischemia
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1791 Sources: http://www.drugbank.ca/drugs/DB00594 |
776.0 nM [IC50] | ||
Target ID: P51168 Gene ID: 6338.0 Gene Symbol: SCNN1B Target Organism: Homo sapiens (Human) Sources: http://www.drugbank.ca/drugs/DB00594 |
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Target ID: P51170|||Q96TD2 Gene ID: 6340.0 Gene Symbol: SCNN1G Target Organism: Homo sapiens (Human) Sources: http://www.drugbank.ca/drugs/DB00594 |
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Target ID: CHEMBL5368 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19339181 |
4.4 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Midamor Approved UsePreventing development of low blood potassium or helping to restore normal blood potassium in patients with high blood pressure or heart failure. Launch Date1981 |
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Primary | Midamor Approved UsePreventing development of low blood potassium or helping to restore normal blood potassium in patients with high blood pressure or heart failure. Launch Date1981 |
Cmax
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 |
T1/2
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 |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
77% |
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: Page: p.372 |
healthy, 25-44 n = 5 Health Status: healthy Age Group: 25-44 Sex: M Population Size: 5 Sources: Page: p.372 |
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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%) Sources: Page: p.696Constipation (5.5%) Malaise (moderate, 5.5%) |
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%) Sources: Page: p.423Weakness (severe, 16.7%) |
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: 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 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
likely | ||||
weak [IC50 1091 uM] | ||||
weak [IC50 840 uM] | ||||
yes [IC50 2.41 uM] | ||||
yes [IC50 3.06 uM] | ||||
yes [IC50 62 uM] | ||||
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes | ||||
yes | ||||
yes | ||||
yes |
PubMed
Title | Date | PubMed |
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Inhibition of pig liver and Zea mays L. polyamine oxidase: a comparative study. | 2001 |
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Regulation of tubular cell MCP-1 production by intracellular ions: a role for sodium and calcium. | 2001 |
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Response of alkalinization or acidification by phytohemagglutinin is dependent on the activity of protein kinase C in human peripheral T Cells. | 2001 |
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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 |
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Hypertonicity stimulates Cl(-) transport in the intestine of fresh water acclimated eel, Anguilla anguilla. | 2001 |
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Impaired sodium excretion, decreased glomerular filtration rate and elevated blood pressure in endothelin receptor type B deficient rats. | 2001 |
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Maxi K+ channels co-localised with CFTR in the apical membrane of an exocrine gland acinus: possible involvement in secretion. | 2001 Apr |
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Regulation of Na(+) transport across leech skin by peptide hormones and neurotransmitters. | 2001 Apr |
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Effects of SNP, ouabain, and amiloride on electrical potential profile of isolated sheep pleura. | 2001 Apr |
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Contribution of amiloride-insensitive pathways to alveolar fluid clearance in adult rats. | 2001 Apr |
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Characterization of stretch-activated cation current in coronary smooth muscle cells. | 2001 Apr |
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Platelet hyperactivity and abnormal Ca(2+) homeostasis in diabetes mellitus. | 2001 Apr |
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Oxygen-evoked Na+ transport in rat fetal distal lung epithelial cells. | 2001 Apr 1 |
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Effect of 2',4'-dichlorobenzamil hydrochloride, a Na(+)-Ca(2+) exchange inhibitor, on human spermatozoa. | 2001 Apr 20 |
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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 |
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Angiotensin II type I receptor modulates intracellular free Mg2+ in renally derived cells via Na+-dependent Ca2+-independent mechanisms. | 2001 Apr 27 |
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Na(+)-dependent pH regulation by the amitochondriate protozoan parasite Giardia intestinalis. | 2001 Aug 3 |
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Beta1-adrenergic agonist is a potent stimulator of alveolar fluid clearance in hyperoxic rat lungs. | 2001 Feb |
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Oral irritation by sodium chloride: sensitization, self-desensitization, and cross-sensitization to capsaicin. | 2001 Feb |
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Involvement of calcium influx in hypoxia-induced bleb formation in human umbilical vein endothelial cells. | 2001 Feb-Mar |
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Na+-dependent recovery of intracellular pH from acid loading in mouse colonic crypt cells. | 2001 Jan |
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Isolated working rat heart adaptation after abrupt changes in extracellular Ca2+ concentration. | 2001 Jan |
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Activation of epithelial sodium channels by prostasin in Xenopus oocytes. | 2001 Jun |
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NHE and ICAM-1 expression in hypoxic/reoxygenated coronary microvascular endothelial cells. | 2001 Jun |
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cAMP-dependent fluid secretion in rat inner medullary collecting ducts. | 2001 Jun |
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Epithelial Na(+) channels are regulated by flow. | 2001 Jun |
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Acute adaptive cellular base uptake in rat duodenal epithelium. | 2001 Jun |
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Mechanisms of TNF-alpha stimulation of amiloride-sensitive sodium transport across alveolar epithelium. | 2001 Jun |
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Bafilomycin A(1) inhibits rhinovirus infection in human airway epithelium: effects on endosome and ICAM-1. | 2001 Jun |
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Protease-activated receptor-2-mediated inhibition of ion transport in human bronchial epithelial cells. | 2001 Jun |
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Effects of SM-20550, a selective Na+-H+ exchange inhibitor, on the ion transport of myocardial mitochondria. | 2001 Mar |
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Subtypes of low voltage-activated Ca2+ channels in laterodorsal thalamic neurons: possible localization and physiological roles. | 2001 Mar |
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NaCl detection thresholds: comparison of Fischer 344 and Wistar rats. | 2001 Mar |
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New quinolone, grepafloxacin, inhibits Cl- secretion across bovine airway epithelium in culture. | 2001 Mar |
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The use of a response surface methodology on HPLC analysis of methyldopa, amiloride and hydrochlorothiazide in tablets. | 2001 Mar |
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The essential role of cytosolic Cl- in Ca2+ regulation of an amiloride-sensitive channel in fetal rat pneumocyte. | 2001 Mar 1 |
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Gramicidin-perforated patch analysis on HCO3- secretion through a forskolin-activated anion channel in rat parotid intralobular duct cells. | 2001 Mar 1 |
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L-arginine effects on Na+ transport in M-1 mouse cortical collecting duct cells--a cationic amino acid absorbing epithelium. | 2001 Mar 15 |
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Inhibition of Na+-H+ exchanger-3 interferes with apical receptor-mediated endocytosis via vesicle fusion. | 2001 Mar 15 |
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No-flow ischemia inhibits insulin signaling in heart by decreasing intracellular pH. | 2001 Mar 16 |
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[Lithium intoxication due to simultaneous use of trimethoprim]. | 2001 Mar 17 |
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Endothelin-1 has a unique oxygen-saving effect by increasing contractile efficiency in the isolated rat heart. | 2001 Mar 20 |
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Lung epithelial ion transport in neonatal lung disease. | 2001 May |
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Alveolar epithelial barrier functions in ventilated perfused rabbit lungs. | 2001 May |
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Nongenomic effect of testosterone on chloride secretion in cultured rat efferent duct epithelia. | 2001 May |
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Simultaneous direct determination of amiloride and triamterene in urine using isopotential fluorometry. | 2001 May 1 |
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Dependence of the acid-sensitive ion channel, ASIC1a, on extracellular Ca(2+) ions. | 2001 May 11 |
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Molecular cloning and characterization of a novel (Na+,K+)/H+ exchanger localized to the trans-Golgi network. | 2001 May 18 |
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A standing Na+ conductance in rat carotid body type I cells. | 2001 May 25 |
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Amiloride-sensitive sodium currents in identified taste cells of the frog. | 2001 May 25 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/dosage/midamor.html
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25864651
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.
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C49186
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FDA ORPHAN DRUG |
48190
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EU-Orphan Drug |
EU/3/03/147
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NCI_THESAURUS |
C582
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68540
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CHEMBL945
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142424
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84743
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755847
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m1671
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AMILORIDE HYDROCHLORIDE
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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. | ||
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SUB00445MIG
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FZJ37245UC
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SUB21895
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100000088483
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DTXSID80169826
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1019701
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DBSALT001807
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17440-83-4
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C47390
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ACTIVE MOIETY
SUBSTANCE RECORD