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Identification
NameAmiloride
Accession NumberDB00594  (APRD00790, EXPT00514)
TypeSmall Molecule
GroupsApproved
Description

A pyrazine compound inhibiting sodium reabsorption through sodium channels in renal epithelial cells. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with diuretics to spare potassium loss. (From Gilman et al., Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 9th ed, p705)

Structure
Thumb
Synonyms
3,5-Diamino-N-carbamimidoyl-6-chloropyrazine-2-carboxamide
Amilorid
Amilorida
Amiloridum
Amipramidin
Amipramidine
Amyloride
N-amidino-3,5-diamino-6-chloropyrazinecarboxamide
External Identifiers
  • MK 870
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Amiloride Hydrochloridetablet5 mg/1oralPhysicians Total Care, Inc.2005-01-28Not applicableUs
Amiloride Hydrochloride Tablets, USPtablet5 mgoralOrbus Pharma IncNot applicableNot applicableCanada
Amiloride Hydrocloridetablet5 mg/1oralPaddock Laboratories, LLC2009-04-06Not applicableUs
Midamortablet5.0 mgoralAa Pharma Inc2004-06-18Not applicableCanada
Midamor Tablets 5mgtablet5 mgoralOrbus Pharma Inc1981-12-312010-06-16Canada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Amiloride Hydrochloridetablet5 mg/1oralAv Kare, Inc.2012-03-28Not applicableUs
Amiloride Hydrochloridetablet5 mg/1oralCarilion Materials Management1986-01-22Not applicableUs
Amiloride Hydrochloridetablet5 mg/1oralGolden State Medical Supply, Inc.2015-08-31Not applicableUs
Amiloride Hydrochloridetablet5 mg/1oralPar Pharmaceutical Inc.1986-01-22Not applicableUs
Amiloride Hydrochloridetablet5 mg/1oralZydus Pharmaceuticals (USA) Inc.2015-09-14Not applicableUs
Amiloride Hydrochloridetablet5 mg/1oralCadila Healthcare Limited2015-09-14Not applicableUs
Amiloride Hydrochloridetablet5 mg/1oralRising Pharmaceuticals, Inc2009-05-01Not applicableUs
Amiloride Hydrochloridetablet5 mg/1oralAv Pak2013-01-28Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
ArumilSharp & Dohme
KalurilAlphapharm
ModamideMerck
ModureticMerck
Brand mixtures
NameLabellerIngredients
Alti-amiloride HctzAltimed Pharma Inc.
Ami-hydro TabPro Doc Limitee
Amiloride Hydrochloride and HydrochlorothiazideMylan Pharmaceuticals Inc.
Apo-amilzide TabApotex Inc
ModuretPrempharm Inc
Mylan-amilazideMylan Pharmaceuticals Ulc
NovamilorTeva Canada Limited
Nu-amilzide 5/50 Mg TabNu Pharm Inc
Penta-amiloride Hctz TabletsPentapharm Ltd.
Riva-amilzide 5/50 mgLaboratoire Riva Inc
Salts
Name/CASStructureProperties
Amiloride hydrochloride
2016-88-8
Thumb
  • InChI Key: ACHKKGDWZVCSNH-UHFFFAOYSA-N
  • Monoisotopic Mass: 265.0245633
  • Average Mass: 266.09
DBSALT001807
Amiloride hydrochloride dihydrate
17440-83-4
Thumb
  • InChI Key: LTKVFMLMEYCWMK-UHFFFAOYSA-N
  • Monoisotopic Mass: 301.045692731
  • Average Mass: 302.119
DBSALT000270
Categories
UNII7DZO8EB0Z3
CAS number2609-46-3
WeightAverage: 229.627
Monoisotopic: 229.04788562
Chemical FormulaC6H8ClN7O
InChI KeyInChIKey=XSDQTOBWRPYKKA-UHFFFAOYSA-N
InChI
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)
IUPAC Name
3,5-diamino-6-chloro-N-(diaminomethylidene)pyrazine-2-carboxamide
SMILES
NC(N)=NC(=O)C1=C(N)N=C(N)C(Cl)=N1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as pyrazinecarboxamides. These are compounds containing a pyrazine ring which bears a carboxamide.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazines
Sub ClassPyrazines
Direct ParentPyrazinecarboxamides
Alternative Parents
Substituents
  • Pyrazinecarboxamide
  • Aminopyrazine
  • Acylguanidine
  • Imidolactam
  • Primary aromatic amine
  • Aryl halide
  • Aryl chloride
  • Heteroaromatic compound
  • Vinylogous amide
  • Guanidine
  • Carboxamide group
  • Azacycle
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboximidamide
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor use as adjunctive treatment with thiazide diuretics or other kaliuretic-diuretic agents in congestive heart failure or hypertension.
PharmacodynamicsAmiloride, 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. The risk is high in concurrent use of ACE inhibitors or spironolactone. Patients are also advised not to use potassium-containing salt replacements.
Mechanism of actionAmiloride 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. Amiloride exerts its potassium sparing effect through the inhibition of sodium reabsorption at the distal convoluted tubule, cortical collecting tubule and collecting duct; this decreases the net negative potential of the tubular lumen and reduces both potassium and hydrogen secretion and their subsequent excretion. Amiloride is not an aldosterone antagonist and its effects are seen even in the absence of aldosterone.
Related Articles
AbsorptionReadily absorbed following oral administration.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Amiloride is not metabolized by the liver but is excreted unchanged by the kidneys.

Route of eliminationAmiloride HCl is not metabolized by the liver but is excreted unchanged by the kidneys. About 50 percent of a 20 mg dose of amiloride HCl is excreted in the urine and 40 percent in the stool within 72 hours.
Half lifePlasma half-life varies from 6 to 9 hours.
ClearanceNot Available
ToxicityNo data are available in regard to overdosage in humans. The oral LD50 of amiloride hydrochloride (calculated as the base) is 56 mg/kg in mice and 36 to 85 mg/kg in rats, depending on the strain. The most likely signs and symptoms to be expected with overdosage are dehydration and electrolyte imbalance.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Amiloride Action PathwayDrug actionSMP00133
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9408
Blood Brain Barrier+0.7193
Caco-2 permeable-0.8957
P-glycoprotein substrateNon-substrate0.7207
P-glycoprotein inhibitor INon-inhibitor0.9282
P-glycoprotein inhibitor IINon-inhibitor0.9677
Renal organic cation transporterNon-inhibitor0.8122
CYP450 2C9 substrateNon-substrate0.8253
CYP450 2D6 substrateNon-substrate0.8778
CYP450 3A4 substrateNon-substrate0.6687
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9577
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9295
CYP450 3A4 inhibitorNon-inhibitor0.9733
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9605
Ames testAMES toxic0.9107
CarcinogenicityNon-carcinogens0.9119
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5469 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9838
hERG inhibition (predictor II)Non-inhibitor0.8945
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Par pharmaceutical inc
  • Sigmapharm laboratories llc
  • Paddock laboratories inc
Packagers
Dosage forms
FormRouteStrength
Tabletoral
Tabletoral5 mg/1
Tabletoral5.0 mg
Tabletoral5 mg
Prices
Unit descriptionCostUnit
Amiloride hcl powder5.6USD g
Amiloride hcl 5 mg tablet1.49USD tablet
Midamor 5 mg tablet1.19USD tablet
Apo-Amiloride 5 mg Tablet0.28USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point240.5-241.5Cragoe, E.J., Jr.; US. Patent 3,313,813; April 11,1967; assigned to Merck 81 Co., Inc.
water solubilitySlightly solubleNot Available
logP-0.3Not Available
pKa8.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility1.22 mg/mLALOGPS
logP-0.72ALOGPS
logP-0.89ChemAxon
logS-2.3ALOGPS
pKa (Strongest Acidic)16.46ChemAxon
pKa (Strongest Basic)3.29ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area159.29 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity56.69 m3·mol-1ChemAxon
Polarizability19.99 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
References
Synthesis Reference

Cragoe, E.J., Jr.; US. Patent 3,313,813; April 11,1967; assigned to Merck 81 Co., Inc.

General ReferencesNot Available
External Links
ATC CodesC03DB01
AHFS Codes
  • 40:28.16
PDB Entries
FDA labelDownload (377 KB)
MSDSDownload (39.3 KB)
Interactions
Drug Interactions
Drug
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Acetylsalicylic acid is combined with Amiloride.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Amiloride.
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Amiloride.
AlfuzosinAlfuzosin may increase the hypotensive activities of Amiloride.
AmifostineAmiloride may increase the hypotensive activities of Amifostine.
Ammonium chlorideThe risk or severity of adverse effects can be increased when Amiloride is combined with Ammonium chloride.
ArdeparinArdeparin may increase the hyperkalemic activities of Amiloride.
BrimonidineBrimonidine may increase the antihypertensive activities of Amiloride.
BuprenorphineThe risk or severity of adverse effects can be increased when Buprenorphine is combined with Amiloride.
BupropionThe serum concentration of Amiloride can be increased when it is combined with Bupropion.
ButabarbitalButabarbital may increase the hypotensive activities of Amiloride.
ButethalButethal may increase the hypotensive activities of Amiloride.
ButorphanolThe risk or severity of adverse effects can be increased when Butorphanol is combined with Amiloride.
CaffeineThe risk or severity of adverse effects can be increased when Caffeine is combined with Amiloride.
CanagliflozinCanagliflozin may increase the hyperkalemic activities of Amiloride.
ChlorphenamineThe risk or severity of adverse effects can be increased when Chlorphenamine is combined with Amiloride.
CodeineThe risk or severity of adverse effects can be increased when Codeine is combined with Amiloride.
CyclosporineAmiloride may increase the hyperkalemic activities of Cyclosporine.
DiazoxideDiazoxide may increase the hypotensive activities of Amiloride.
DigoxinThe therapeutic efficacy of Digoxin can be decreased when used in combination with Amiloride.
DihydrocodeineThe risk or severity of adverse effects can be increased when Dihydrocodeine is combined with Amiloride.
DofetilideThe serum concentration of Dofetilide can be increased when it is combined with Amiloride.
DrospirenoneDrospirenone may increase the hyperkalemic activities of Amiloride.
DuloxetineAmiloride may increase the orthostatic hypotensive activities of Duloxetine.
EplerenoneEplerenone may increase the hyperkalemic activities of Amiloride.
FentanylThe risk or severity of adverse effects can be increased when Fentanyl is combined with Amiloride.
HeparinHeparin may increase the hyperkalemic activities of Amiloride.
HeptabarbitalHeptabarbital may increase the hypotensive activities of Amiloride.
HexobarbitalHexobarbital may increase the hypotensive activities of Amiloride.
HydrocodoneThe risk or severity of adverse effects can be increased when Hydrocodone is combined with Amiloride.
HydromorphoneThe risk or severity of adverse effects can be increased when Hydromorphone is combined with Amiloride.
InfliximabInfliximab may decrease the antihypertensive activities of Amiloride.
LevodopaAmiloride may increase the orthostatic hypotensive activities of Levodopa.
LevorphanolThe risk or severity of adverse effects can be increased when Levorphanol is combined with Amiloride.
MethadoneThe risk or severity of adverse effects can be increased when Methadone is combined with Amiloride.
MethohexitalMethohexital may increase the hypotensive activities of Amiloride.
MethylphenidateMethylphenidate may decrease the antihypertensive activities of Amiloride.
MolsidomineMolsidomine may increase the hypotensive activities of Amiloride.
MorphineThe risk or severity of adverse effects can be increased when Morphine is combined with Amiloride.
MoxonidineMoxonidine may increase the hypotensive activities of Amiloride.
NalbuphineThe risk or severity of adverse effects can be increased when Nalbuphine is combined with Amiloride.
NicorandilNicorandil may increase the hypotensive activities of Amiloride.
ObinutuzumabAmiloride may increase the hypotensive activities of Obinutuzumab.
OxycodoneThe risk or severity of adverse effects can be increased when Oxycodone is combined with Amiloride.
OxymorphoneThe risk or severity of adverse effects can be increased when Oxymorphone is combined with Amiloride.
PentazocineThe risk or severity of adverse effects can be increased when Pentazocine is combined with Amiloride.
PentobarbitalPentobarbital may increase the hypotensive activities of Amiloride.
PentoxifyllinePentoxifylline may increase the hypotensive activities of Amiloride.
PerindoprilAmiloride may increase the hyperkalemic activities of Perindopril.
PethidineThe risk or severity of adverse effects can be increased when Pethidine is combined with Amiloride.
PhenelzinePhenelzine may increase the orthostatic hypotensive activities of Amiloride.
PrimidonePrimidone may increase the hypotensive activities of Amiloride.
QuinidineThe therapeutic efficacy of Quinidine can be decreased when used in combination with Amiloride.
QuinineQuinine may increase the hypotensive activities of Amiloride.
RemifentanilThe risk or severity of adverse effects can be increased when Remifentanil is combined with Amiloride.
RisperidoneAmiloride may increase the hypotensive activities of Risperidone.
RituximabAmiloride may increase the hypotensive activities of Rituximab.
SecobarbitalSecobarbital may increase the hypotensive activities of Amiloride.
SpironolactoneAmiloride may increase the hyperkalemic activities of Spironolactone.
SufentanilThe risk or severity of adverse effects can be increased when Sufentanil is combined with Amiloride.
TacrolimusAmiloride may increase the hyperkalemic activities of Tacrolimus.
TadalafilTadalafil may increase the antihypertensive activities of Amiloride.
TapentadolThe risk or severity of adverse effects can be increased when Tapentadol is combined with Amiloride.
TolvaptanTolvaptan may increase the hyperkalemic activities of Amiloride.
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Amiloride.
TranylcypromineTranylcypromine may increase the orthostatic hypotensive activities of Amiloride.
TreprostinilTreprostinil may increase the hypotensive activities of Amiloride.
ValsartanValsartan may increase the hyperkalemic activities of Amiloride.
VardenafilVardenafil may increase the antihypertensive activities of Amiloride.
YohimbineYohimbine may decrease the antihypertensive activities of Amiloride.
Food Interactions
  • Avoid drastic changes in dietary habit.
  • Avoid natural licorice.
  • Avoid salt substitutes containing potassium.
  • Take with food to reduce irritation.

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Ww domain binding
Specific Function:
Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Plays an essential role in electrolyte and blood pressure homeostasis, but also in airway surface liquid homeostasis, which is important for proper clearance of mucus. C...
Gene Name:
SCNN1A
Uniprot ID:
P37088
Molecular Weight:
75703.08 Da
References
  1. Kelly O, Lin C, Ramkumar M, Saxena NC, Kleyman TR, Eaton DC: Characterization of an amiloride binding region in the alpha-subunit of ENaC. Am J Physiol Renal Physiol. 2003 Dec;285(6):F1279-90. Epub 2003 Aug 19. [PubMed:12928313 ]
  2. Ji HL, Benos DJ: Degenerin sites mediate proton activation of deltabetagamma-epithelial sodium channel. J Biol Chem. 2004 Jun 25;279(26):26939-47. Epub 2004 Apr 14. [PubMed:15084585 ]
  3. Otulakowski G, Duan W, Gandhi S, O'brodovich H: Steroid and oxygen effects on eIF4F complex, mTOR, and ENaC translation in fetal lung epithelia. Am J Respir Cell Mol Biol. 2007 Oct;37(4):457-66. Epub 2007 Jun 7. [PubMed:17556672 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Ww domain binding
Specific Function:
Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Plays an essential role in electrolyte and blood pressure homeostasis, but also in airway surface liquid homeostasis, which is important for proper clearance of mucus. C...
Gene Name:
SCNN1B
Uniprot ID:
P51168
Molecular Weight:
72658.485 Da
References
  1. Lebowitz J, An B, Edinger RS, Zeidel ML, Johnson JP: Effect of altered Na+ entry on expression of apical and basolateral transport proteins in A6 epithelia. Am J Physiol Renal Physiol. 2003 Sep;285(3):F524-31. Epub 2003 May 13. [PubMed:12746257 ]
  2. Planes C, Leyvraz C, Uchida T, Angelova MA, Vuagniaux G, Hummler E, Matthay M, Clerici C, Rossier B: In vitro and in vivo regulation of transepithelial lung alveolar sodium transport by serine proteases. Am J Physiol Lung Cell Mol Physiol. 2005 Jun;288(6):L1099-109. Epub 2005 Jan 28. [PubMed:15681398 ]
  3. Yamagata T, Yamagata Y, Nishimoto T, Nakanishi M, Nakanishi H, Minakata Y, Mune M, Yukawa S: The impact of phorbol ester on the regulation of amiloride-sensitive epithelial sodium channel in alveolar type ii epithelial cells. Exp Lung Res. 2002 Oct-Nov;28(7):543-62. [PubMed:12396248 ]
  4. Brooks HL, Allred AJ, Beutler KT, Coffman TM, Knepper MA: Targeted proteomic profiling of renal Na(+) transporter and channel abundances in angiotensin II type 1a receptor knockout mice. Hypertension. 2002 Feb;39(2 Pt 2):470-3. [PubMed:11882592 ]
  5. Kamide K, Tanaka C, Takiuchi S, Miwa Y, Yoshii M, Horio T, Kawano Y, Miyata T: Six missense mutations of the epithelial sodium channel beta and gamma subunits in Japanese hypertensives. Hypertens Res. 2004 May;27(5):333-8. [PubMed:15198480 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Ww domain binding
Specific Function:
Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Plays an essential role in electrolyte and blood pressure homeostasis, but also in airway surface liquid homeostasis, which is important for proper clearance of mucus. C...
Gene Name:
SCNN1G
Uniprot ID:
P51170
Molecular Weight:
74269.62 Da
References
  1. Viemann M, Peter M, Lopez-Siguero JP, Simic-Schleicher G, Sippell WG: Evidence for genetic heterogeneity of pseudohypoaldosteronism type 1: identification of a novel mutation in the human mineralocorticoid receptor in one sporadic case and no mutations in two autosomal dominant kindreds. J Clin Endocrinol Metab. 2001 May;86(5):2056-9. [PubMed:11344206 ]
  2. Iwai N, Baba S, Mannami T, Katsuya T, Higaki J, Ogihara T, Ogata J: Association of sodium channel gamma-subunit promoter variant with blood pressure. Hypertension. 2001 Jul;38(1):86-9. [PubMed:11463765 ]
  3. Yamagata T, Yamagata Y, Nishimoto T, Nakanishi M, Nakanishi H, Minakata Y, Mune M, Yukawa S: The impact of phorbol ester on the regulation of amiloride-sensitive epithelial sodium channel in alveolar type ii epithelial cells. Exp Lung Res. 2002 Oct-Nov;28(7):543-62. [PubMed:12396248 ]
  4. Akcay A, Yavuz T, Semiz S, Bundak R, Demirdoven M: Pseudohypoaldosteronism type 1 and respiratory distress syndrome. J Pediatr Endocrinol Metab. 2002 Nov-Dec;15(9):1557-61. [PubMed:12503866 ]
  5. Ludwig M, Bidlingmaier F, Reissinger A: Pseudohypoaldosteronism type 1 and the genes encoding prostasin, alpha-spectrin, and Nedd4. Int J Mol Med. 2004 Dec;14(6):1101-4. [PubMed:15547682 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Ligand-gated sodium channel activity
Specific Function:
Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. Also plays a role in taste perception.
Gene Name:
SCNN1D
Uniprot ID:
P51172
Molecular Weight:
70214.195 Da
References
  1. Yamamura H, Ugawa S, Ueda T, Nagao M, Shimada S: Protons activate the delta-subunit of the epithelial Na+ channel in humans. J Biol Chem. 2004 Mar 26;279(13):12529-34. Epub 2004 Jan 15. [PubMed:14726523 ]
  2. Ji HL, Bishop LR, Anderson SJ, Fuller CM, Benos DJ: The role of Pre-H2 domains of alpha- and delta-epithelial Na+ channels in ion permeation, conductance, and amiloride sensitivity. J Biol Chem. 2004 Feb 27;279(9):8428-40. Epub 2003 Dec 2. [PubMed:14660613 ]
  3. Ji HL, Su XF, Kedar S, Li J, Barbry P, Smith PR, Matalon S, Benos DJ: Delta-subunit confers novel biophysical features to alpha beta gamma-human epithelial sodium channel (ENaC) via a physical interaction. J Biol Chem. 2006 Mar 24;281(12):8233-41. Epub 2006 Jan 19. [PubMed:16423824 ]
  4. Yamamura H, Ugawa S, Ueda T, Nagao M, Shimada S: Icilin activates the delta-subunit of the human epithelial Na+ channel. Mol Pharmacol. 2005 Oct;68(4):1142-7. Epub 2005 Jul 20. [PubMed:16033954 ]
  5. Yamamura H, Ugawa S, Ueda T, Shimada S: Evans blue is a specific antagonist of the human epithelial Na+ channel delta-subunit. J Pharmacol Exp Ther. 2005 Nov;315(2):965-9. Epub 2005 Aug 17. [PubMed:16107516 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Zinc ion binding
Specific Function:
Catalyzes the degradation of compounds such as putrescine, histamine, spermine, and spermidine, substances involved in allergic and immune responses, cell proliferation, tissue differentiation, tumor formation, and possibly apoptosis. Placental DAO is thought to play a role in the regulation of the female reproductive function.
Gene Name:
AOC1
Uniprot ID:
P19801
Molecular Weight:
85377.1 Da
References
  1. Padiglia A, Medda R, Lorrai A, Murgia B, Pedersen JZ, Finazzi Agro A, Floris G: Interaction of Pig Kidney and Lentil Seedling Copper-Containing Amine Oxidases with Guanidinium Compounds. J Enzyme Inhib. 1999 Nov;15(1):91-100. [PubMed:10938536 ]
  2. Padiglia A, Medda R, Lorrai A, Murgia B, Pedersen JZ, Agro AF, Floris G: Interaction of pig kidney and lentil seedling copper-containing amine oxidases with guanidinium compounds. J Enzyme Inhib. 2000;15(1):91-100. [PubMed:10850957 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Ligand-gated sodium channel activity
Specific Function:
Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. Also permeable for Li(+) and K(+). Generates a biphasic current with a fast inactivating and a slow sustained phase. Heteromeric channel assembly seems to modulate.
Gene Name:
ASIC2
Uniprot ID:
Q16515
Molecular Weight:
57708.515 Da
References
  1. Berdiev BK, Xia J, McLean LA, Markert JM, Gillespie GY, Mapstone TB, Naren AP, Jovov B, Bubien JK, Ji HL, Fuller CM, Kirk KL, Benos DJ: Acid-sensing ion channels in malignant gliomas. J Biol Chem. 2003 Apr 25;278(17):15023-34. Epub 2003 Feb 12. [PubMed:12584187 ]
  2. Ugawa S, Yamamoto T, Ueda T, Ishida Y, Inagaki A, Nishigaki M, Shimada S: Amiloride-insensitive currents of the acid-sensing ion channel-2a (ASIC2a)/ASIC2b heteromeric sour-taste receptor channel. J Neurosci. 2003 May 1;23(9):3616-22. [PubMed:12736332 ]
  3. Ugawa S: Identification of sour-taste receptor genes. Anat Sci Int. 2003 Dec;78(4):205-10. [PubMed:14686475 ]
  4. Peng BG, Ahmad S, Chen S, Chen P, Price MP, Lin X: Acid-sensing ion channel 2 contributes a major component to acid-evoked excitatory responses in spiral ganglion neurons and plays a role in noise susceptibility of mice. J Neurosci. 2004 Nov 10;24(45):10167-75. [PubMed:15537887 ]
  5. Vila-Carriles WH, Kovacs GG, Jovov B, Zhou ZH, Pahwa AK, Colby G, Esimai O, Gillespie GY, Mapstone TB, Markert JM, Fuller CM, Bubien JK, Benos DJ: Surface expression of ASIC2 inhibits the amiloride-sensitive current and migration of glioma cells. J Biol Chem. 2006 Jul 14;281(28):19220-32. Epub 2006 May 16. [PubMed:16704974 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Ligand-gated sodium channel activity
Specific Function:
Isoform 2 and isoform 3 function as proton-gated sodium channels; they are activated by a drop of the extracellular pH and then become rapidly desensitized. The channel generates a biphasic current with a fast inactivating and a slow sustained phase. Has high selectivity for sodium ions and can also transport lithium ions with high efficiency. Isoform 2 can also transport potassium, but with lo...
Gene Name:
ASIC1
Uniprot ID:
P78348
Molecular Weight:
59908.915 Da
References
  1. Petruska JC, Napaporn J, Johnson RD, Cooper BY: Chemical responsiveness and histochemical phenotype of electrophysiologically classified cells of the adult rat dorsal root ganglion. Neuroscience. 2002;115(1):15-30. [PubMed:12401318 ]
  2. Jones NG, Slater R, Cadiou H, McNaughton P, McMahon SB: Acid-induced pain and its modulation in humans. J Neurosci. 2004 Dec 1;24(48):10974-9. [PubMed:15574747 ]
  3. Sugiura T, Dang K, Lamb K, Bielefeldt K, Gebhart GF: Acid-sensing properties in rat gastric sensory neurons from normal and ulcerated stomach. J Neurosci. 2005 Mar 9;25(10):2617-27. [PubMed:15758172 ]
  4. Wang W, Duan B, Xu H, Xu L, Xu TL: Calcium-permeable acid-sensing ion channel is a molecular target of the neurotoxic metal ion lead. J Biol Chem. 2006 Feb 3;281(5):2497-505. Epub 2005 Nov 29. [PubMed:16319075 ]
  5. Xiong ZG, Chu XP, Simon RP: Ca2+ -permeable acid-sensing ion channels and ischemic brain injury. J Membr Biol. 2006 Jan;209(1):59-68. Epub 2006 Apr 17. [PubMed:16685601 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Solute:proton antiporter activity
Specific Function:
Involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient. Plays an important role in signal transduction.
Gene Name:
SLC9A1
Uniprot ID:
P19634
Molecular Weight:
90762.13 Da
References
  1. Lee MG, Ahn W, Choi JY, Luo X, Seo JT, Schultheis PJ, Shull GE, Kim KH, Muallem S: Na(+)-dependent transporters mediate HCO(3)(-) salvage across the luminal membrane of the main pancreatic duct. J Clin Invest. 2000 Jun;105(11):1651-8. [PubMed:10841524 ]
  2. Konstantinou-Tegou A, Kaloyianni M, Bourikas D, Koliakos G: The effect of leptin on Na(+)-H(+) antiport (NHE 1) activity of obese and normal subjects erythrocytes. Mol Cell Endocrinol. 2001 Oct 25;183(1-2):11-8. [PubMed:11604219 ]
  3. Serrani RE, Mujica G, Gioia IA, Corchs JL: Neonatal red blood cells: amiloride-insensitive Na+-H+ transport isoform would express Na+-Li+ exchange. Acta Physiol Pharmacol Bulg. 2000;25(3-4):71-4. [PubMed:11688549 ]
  4. Cuthbert AW, Supuran CT, MacVinish LJ: Bicarbonate-dependent chloride secretion in Calu-3 epithelia in response to 7,8-benzoquinoline. J Physiol. 2003 Aug 15;551(Pt 1):79-92. Epub 2003 Jul 18. [PubMed:12872009 ]
  5. Furukawa O, Bi LC, Guth PH, Engel E, Hirokawa M, Kaunitz JD: NHE3 inhibition activates duodenal bicarbonate secretion in the rat. Am J Physiol Gastrointest Liver Physiol. 2004 Jan;286(1):G102-9. Epub 2003 Jul 24. [PubMed:12881227 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Serine-type endopeptidase activity
Specific Function:
Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.
Gene Name:
PLAU
Uniprot ID:
P00749
Molecular Weight:
48507.09 Da
References
  1. Vakili J, Standker L, Detheux M, Vassart G, Forssmann WG, Parmentier M: Urokinase plasminogen activator and plasmin efficiently convert hemofiltrate CC chemokine 1 into its active. J Immunol. 2001 Sep 15;167(6):3406-13. [PubMed:11544332 ]
  2. Jankun J, Skrzypczak-Jankun E: Binding site of amiloride to urokinase plasminogen activator depends on species. Int J Mol Med. 2001 Oct;8(4):365-71. [PubMed:11562773 ]
  3. Luikart S, Masri M, Wahl D, Hinkel T, Beck JM, Gyetko MR, Gupta P, Oegema T: Urokinase is required for the formation of mactinin, an alpha-actinin fragment that promotes monocyte/macrophage maturation. Biochim Biophys Acta. 2002 Aug 19;1591(1-3):99-107. [PubMed:12183060 ]
  4. Chen YX, O'Brien ER: Ethyl isopropyl amiloride inhibits smooth muscle cell proliferation and migration by inducing apoptosis and antagonizing urokinase plasminogen activator activity. Can J Physiol Pharmacol. 2003 Jul;81(7):730-9. [PubMed:12897821 ]
  5. Cejkova J, Cejka C, Zvarova J: Effects of inhibition of urokinase-type plasminogen activator (u-PA) by amiloride in the cornea and tear fluid of eyes irradiated with UVB. Acta Histochem. 2005;107(1):77-86. Epub 2005 Mar 4. [PubMed:15866288 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Zinc ion binding
Specific Function:
Catalyzes the degradation of compounds such as putrescine, histamine, spermine, and spermidine, substances involved in allergic and immune responses, cell proliferation, tissue differentiation, tumor formation, and possibly apoptosis. Placental DAO is thought to play a role in the regulation of the female reproductive function.
Gene Name:
AOC1
Uniprot ID:
P19801
Molecular Weight:
85377.1 Da
References
  1. Padiglia A, Medda R, Lorrai A, Murgia B, Pedersen JZ, Finazzi Agro A, Floris G: Interaction of Pig Kidney and Lentil Seedling Copper-Containing Amine Oxidases with Guanidinium Compounds. J Enzyme Inhib. 1999 Nov;15(1):91-100. [PubMed:10938536 ]
  2. Padiglia A, Medda R, Lorrai A, Murgia B, Pedersen JZ, Agro AF, Floris G: Interaction of pig kidney and lentil seedling copper-containing amine oxidases with guanidinium compounds. J Enzyme Inhib. 2000;15(1):91-100. [PubMed:10850957 ]
Kind
Protein
Organism
Pig
Pharmacological action
unknown
Actions
inhibitor
General Function:
Zinc ion binding
Specific Function:
Catalyzes the degradation of compounds such as putrescine, histamine, spermine, and spermidine, substances involved in allergic and immune responses, cell proliferation, tissue differentiation, tumor formation, and possibly apoptosis.
Gene Name:
AOC1
Uniprot ID:
Q9TRC7
Molecular Weight:
85474.24 Da
References
  1. Padiglia A, Medda R, Lorrai A, Murgia B, Pedersen JZ, Finazzi Agro A, Floris G: Interaction of Pig Kidney and Lentil Seedling Copper-Containing Amine Oxidases with Guanidinium Compounds. J Enzyme Inhib. 1999 Nov;15(1):91-100. [PubMed:10938536 ]
  2. Padiglia A, Medda R, Lorrai A, Murgia B, Pedersen JZ, Agro AF, Floris G: Interaction of pig kidney and lentil seedling copper-containing amine oxidases with guanidinium compounds. J Enzyme Inhib. 2000;15(1):91-100. [PubMed:10850957 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Quaternary ammonium group transmembrane transporter activity
Specific Function:
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridiniu...
Gene Name:
SLC22A2
Uniprot ID:
O15244
Molecular Weight:
62579.99 Da
References
  1. Urakami Y, Okuda M, Masuda S, Akazawa M, Saito H, Inui K: Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules. Pharm Res. 2001 Nov;18(11):1528-34. [PubMed:11758759 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Secondary active organic cation transmembrane transporter activity
Specific Function:
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine...
Gene Name:
SLC22A1
Uniprot ID:
O15245
Molecular Weight:
61153.345 Da
References
  1. Urakami Y, Okuda M, Masuda S, Akazawa M, Saito H, Inui K: Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules. Pharm Res. 2001 Nov;18(11):1528-34. [PubMed:11758759 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Symporter activity
Specific Function:
Sodium-ion dependent, low affinity carnitine transporter. Probably transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Relative uptake activity ratio of carnitine to TEA is 1.78. A key substrate of this transporter seems to be ergothioneine (ET).
Gene Name:
SLC22A4
Uniprot ID:
Q9H015
Molecular Weight:
62154.48 Da
References
  1. Wu X, George RL, Huang W, Wang H, Conway SJ, Leibach FH, Ganapathy V: Structural and functional characteristics and tissue distribution pattern of rat OCTN1, an organic cation transporter, cloned from placenta. Biochim Biophys Acta. 2000 Jun 1;1466(1-2):315-27. [PubMed:10825452 ]
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Drug created on June 13, 2005 07:24 / Updated on May 01, 2016 17:40