Identification

Name
Amiloride
Accession Number
DB00594  (APRD00790, EXPT00514)
Type
Small Molecule
Groups
Approved
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 IDs
MK 870
Product Ingredients
IngredientUNIICASInChI Key
Amiloride hydrochloride7M458Q65S32016-88-8ACHKKGDWZVCSNH-UHFFFAOYSA-N
Amiloride hydrochloride dihydrateFZJ37245UC17440-83-4LTKVFMLMEYCWMK-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Amiloride HydrochlorideTablet5 mg/1OralPhysicians Total Care, Inc.2005-01-28Not applicableUs00574 0292 01 nlmimage10 473aa3f5
Amiloride Hydrochloride Tablets, USPTablet5 mgOralOrbus Pharma IncNot applicableNot applicableCanada
Amiloride HydroclorideTablet5 mg/1OralPaddock Laboratories, LLC2009-04-06Not applicableUs0574 029220180907 15195 rv6e01
Amiloride HydroclorideTablet5 mg/1OralKaiser Foundations Hospitals2017-09-07Not applicableUs
MidamorTablet5.0 mgOralAa Pharma Inc2004-06-18Not applicableCanada
Midamor Tablets 5mgTablet5 mgOralOrbus Pharma Inc1981-12-312010-06-16Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Amiloride HydrochlorideTablet5 mg/1OralCarilion Materials Management1986-01-22Not applicableUs
Amiloride HydrochlorideTablet5 mg/1OralRising Pharmaceuticals2009-05-01Not applicableUs
Amiloride HydrochlorideTablet5 mg/1OralAv Pak2013-01-28Not applicableUs
Amiloride HydrochlorideTablet5 mg/1OralCadila Pharnmaceuticals2015-09-142017-07-19Us
Amiloride HydrochlorideTablet5 mg/1OralPar Pharmaceutical1986-01-22Not applicableUs
Amiloride HydrochlorideTablet5 mg/1OralAv Kare, Inc.2012-03-28Not applicableUs
Amiloride HydrochlorideTablet5 mg/1OralMed Health Pharma LLC2011-05-102012-06-10Us
Amiloride HydrochlorideTablet5 mg/1OralGolden State Medical Supply, Inc.2015-08-31Not applicableUs
Amiloride HydrochlorideTablet5 mg/1OralZydus Pharmaceuticals Usa, Inc.2015-09-142017-07-19Us
MidamorTablet5 mg/1OralPaddock Laboratories, Inc.2009-04-062011-01-31Us
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Alti-amiloride HctzAmiloride hydrochloride (5 mg) + Hydrochlorothiazide (50 mg)TabletOralAltimed Pharma Inc.1995-12-312004-08-03Canada
Ami-hydro TabAmiloride hydrochloride (5 mg) + Hydrochlorothiazide (50 mg)TabletOralPro Doc Limitee1990-12-31Not applicableCanada
Amiloride Hydrochloride and HydrochlorothiazideAmiloride hydrochloride dihydrate (5 mg/1) + Hydrochlorothiazide (50 mg/1)TabletOralA-S Medication Solutions1989-12-01Not applicableUs50090 051320180913 8702 1rektij
Amiloride Hydrochloride and HydrochlorothiazideAmiloride hydrochloride dihydrate (5 mg/1) + Hydrochlorothiazide (50 mg/1)TabletOralA-S Medication Solutions1989-12-012016-01-07Us54569 386920180907 15195 1qnd3zv
Amiloride Hydrochloride and HydrochlorothiazideAmiloride hydrochloride dihydrate (5 mg/1) + Hydrochlorothiazide (50 mg/1)TabletOralMylan Pharmaceuticals Inc.1991-10-31Not applicableUs00378 0577 01 nlmimage10 c339e1ef
Amiloride Hydrochloride and HydrochlorothiazideAmiloride hydrochloride dihydrate (5 mg/1) + Hydrochlorothiazide (50 mg/1)TabletOralMed Health Pharma LLC.2011-06-012012-06-13Us
Amiloride Hydrochloride and HydrochlorothiazideAmiloride hydrochloride dihydrate (5 mg/1) + Hydrochlorothiazide (50 mg/1)TabletOralTeva1989-12-01Not applicableUs00555 0483 02 nlmimage10 002b804c
Amiloride Hydrochloride and HydrochlorothiazideAmiloride hydrochloride dihydrate (5 mg/1) + Hydrochlorothiazide (50 mg/1)TabletOralAvera McKennan Hospital2016-01-262018-07-09Us
Amiloride Hydrochloride and HydrochlorothiazideAmiloride hydrochloride dihydrate (5 mg/1) + Hydrochlorothiazide (50 mg/1)TabletOralPhysicians Total Care, Inc.1996-05-16Not applicableUs54868 066720180907 15195 dzga7w
Apo-amilzide TabAmiloride hydrochloride (5 mg) + Hydrochlorothiazide (50 mg)TabletOralApotex Corporation1989-12-31Not applicableCanada
International/Other Brands
Arumil (Sharp & Dohme) / Kaluril (Alphapharm) / Modamide (Merck) / Moduretic (Merck)
Categories
UNII
7DZO8EB0Z3
CAS number
2609-46-3
Weight
Average: 229.627
Monoisotopic: 229.04788562
Chemical Formula
C6H8ClN7O
InChI Key
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

Pharmacology

Indication

For use as adjunctive treatment with thiazide diuretics or other kaliuretic-diuretic agents in congestive heart failure or hypertension.

Associated Conditions
Pharmacodynamics

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. 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 action

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. 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.

TargetActionsOrganism
AAmiloride-sensitive sodium channel subunit alpha
inhibitor
Human
AAmiloride-sensitive sodium channel subunit beta
inhibitor
Human
AAmiloride-sensitive sodium channel subunit gamma
inhibitor
Human
AAmiloride-sensitive sodium channel subunit delta
inhibitor
Human
UAmiloride-sensitive amine oxidase [copper-containing]
inhibitor
Human
UAcid-sensing ion channel 2
inhibitor
Human
UAcid-sensing ion channel 1
inhibitor
Human
USodium/hydrogen exchanger 1
inhibitor
Human
UUrokinase-type plasminogen activator
inhibitor
Human
Absorption

Readily absorbed following oral administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

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

Route of elimination

Amiloride 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 life

Plasma half-life varies from 6 to 9 hours.

Clearance
Not Available
Toxicity

No 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
PathwayCategory
Amiloride Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbacavirAmiloride may increase the excretion rate of Abacavir which could result in a lower serum level and potentially a reduction in efficacy.
AcarboseAmiloride may increase the excretion rate of Acarbose which could result in a lower serum level and potentially a reduction in efficacy.
AcebutololThe risk or severity of hyperkalemia can be increased when Amiloride is combined with Acebutolol.
AceclofenacThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Aceclofenac is combined with Amiloride.
AcemetacinThe therapeutic efficacy of Amiloride can be decreased when used in combination with Acemetacin.
AcetaminophenAmiloride may increase the excretion rate of Acetaminophen which could result in a lower serum level and potentially a reduction in efficacy.
AcetyldigitoxinAmiloride may decrease the excretion rate of Acetyldigitoxin which could result in a higher serum level.
AcetyldigoxinAmiloride may decrease the excretion rate of Acetyldigoxin which could result in a higher serum level.
Acetylsalicylic acidThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Acetylsalicylic acid is combined with Amiloride.
AclidiniumAmiloride may increase the excretion rate of Aclidinium which could result in a lower serum level and potentially a reduction in efficacy.
Food Interactions
  • Avoid drastic changes in dietary habit.
  • Avoid natural licorice.
  • Avoid salt substitutes containing potassium.
  • Take with food to reduce irritation.

References

Synthesis Reference

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

General References
Not Available
External Links
Human Metabolome Database
HMDB0014732
KEGG Drug
D07447
KEGG Compound
C06821
PubChem Compound
16231
PubChem Substance
46508156
ChemSpider
15403
BindingDB
16173
ChEBI
2639
ChEMBL
CHEMBL945
Therapeutic Targets Database
DAP000187
PharmGKB
PA448368
IUPHAR
2421
Guide to Pharmacology
GtP Drug Page
HET
AMR
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Amiloride
ATC Codes
C03DB01 — Amiloride
AHFS Codes
  • 40:28.16 — Potassium-sparing Diuretics
PDB Entries
1f5l / 4ntx
FDA label
Download (377 KB)
MSDS
Download (39.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0TerminatedHealth Services ResearchHigh Blood Pressure (Hypertension) / Proteinuria / Type 2 Diabetes Mellitus1
0TerminatedTreatmentAttention Deficit Disorder With Hyperactivity (ADHD)1
1CompletedTreatmentCystic Fibrosis (CF)1
1CompletedTreatmentGastro-esophageal Reflux Disease (GERD) / Heartburn1
1CompletedTreatmentHigh Blood Pressure (Hypertension)2
2Active Not RecruitingTreatmentSecondary Progressive Multiple Sclerosis (SPMS)1
2CompletedNot AvailableCystic Fibrosis (CF)1
2CompletedTreatmentDisseminated Sclerosis / Optic Neuritis1
2RecruitingTreatmentAlbuminuria / Chronic Kidney Disease (CKD)1
2RecruitingTreatmentAutosomal Dominant Hypocalcemia / Autosomal Dominant Hypocalcemia or OR Primary Hypoparathyroidism Related to Other Cause But Complicated by Hypercalciuria Under Treatment1
2, 3CompletedTreatmentCoronary Heart Disease (CHD)1
2, 3RecruitingTreatmentPrimary Hyperparathyroidism1
2, 3Unknown StatusTreatmentCoronary Artery Disease1
3CompletedTreatmentHigh Blood Pressure (Hypertension) / Obstructive Sleep Apnea (OSA)1
4Active Not RecruitingTreatmentHigh Blood Pressure (Hypertension)1
4CompletedTreatmentChronic Kidney Disease (CKD)1
4CompletedTreatmentHigh Blood Pressure (Hypertension)1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Microalbuminuria / Type 2 Diabetes Mellitus1
4RecruitingTreatmentChronic Kidney Disease (CKD)1
4RecruitingTreatmentHigh Blood Pressure (Hypertension)1
4RecruitingTreatmentHypertension Resistant To Conventional Therapy1
4RecruitingTreatmentProteinuria1
4TerminatedTreatmentAtherosclerosis1
4Unknown StatusTreatmentHypertension,Essential1
4Unknown StatusTreatmentPrehypertension1
Not AvailableCompletedNot AvailableFractures, Bone / Type 2 Diabetes Mellitus1
Not AvailableCompletedBasic SciencePhysiological Conditions1
Not AvailableCompletedTreatmentCystic Fibrosis (CF)1
Not AvailableCompletedTreatmentHypertension,Essential1
Not AvailableCompletedTreatmentNephrogenic Diabetes Insipidus1
Not AvailableTerminatedTreatmentHigh Blood Pressure (Hypertension) / Microvascular Angina1
Not AvailableUnknown StatusBasic ScienceDiabetic Nephropathies / High Blood Pressure (Hypertension)1
Not AvailableWithdrawnTreatmentHigh Blood Pressure (Hypertension)1

Pharmacoeconomics

Manufacturers
  • Par pharmaceutical inc
  • Sigmapharm laboratories llc
  • Paddock laboratories inc
Packagers
  • Kaiser Foundation Hospital
  • Paddock Labs
  • Par Pharmaceuticals
  • Physicians Total Care Inc.
  • Qualitest
  • Rising Pharmaceuticals
  • Sigmapharm Laboratories LLC
  • Spectrum Pharmaceuticals
Dosage forms
FormRouteStrength
TabletOral5 mg/1
TabletOral
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.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)240.5-241.5Cragoe, 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 FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-001i-0090000000-d84da076a3897e6fdb4a
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0089-1790000000-9f966f1f1f39d074086a
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00di-3900000000-9e3a3741c916f113d456
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-02tc-5900000000-f32cb47ea7e98516befc
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-02t9-8900000000-7f66a60319e15df262c2
LC-MS/MS Spectrum - LC-ESI-IT , positiveLC-MS/MSsplash10-00dr-1910000000-f028ae70e2d968afae25
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0089-0980000000-a00ea7cb3998c0a8cd77

Taxonomy

Description
This compound belongs to the class of organic compounds known as aminopyrazines. These are organic compounds containing an amino group attached to a pyrazine ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazines
Sub Class
Pyrazines
Direct Parent
Aminopyrazines
Alternative Parents
Imidolactams / Aryl chlorides / Heteroaromatic compounds / Propargyl-type 1,3-dipolar organic compounds / Carboximidamides / Azacyclic compounds / Primary amines / Organopnictogen compounds / Organooxygen compounds / Organochlorides
show 2 more
Substituents
Aminopyrazine / Aryl chloride / Aryl halide / Imidolactam / Heteroaromatic compound / Carboximidamide / Azacycle / Organic 1,3-dipolar compound / Propargyl-type 1,3-dipolar organic compound / Amine
show 11 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
pyrazines, monocarboxylic acid amide, organochlorine compound, guanidines, aromatic amine (CHEBI:2639) / a small molecule (CPD-10324)

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...
Gene Name
SCNN1A
Uniprot ID
P37088
Uniprot Name
Amiloride-sensitive sodium channel subunit alpha
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...
Gene Name
SCNN1B
Uniprot ID
P51168
Uniprot Name
Amiloride-sensitive sodium channel subunit beta
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...
Gene Name
SCNN1G
Uniprot ID
P51170
Uniprot Name
Amiloride-sensitive sodium channel subunit gamma
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...
Gene Name
SCNN1D
Uniprot ID
P51172
Uniprot Name
Amiloride-sensitive sodium channel subunit delta
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, tum...
Gene Name
AOC1
Uniprot ID
P19801
Uniprot Name
Amiloride-sensitive amine oxidase [copper-containing]
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...
Gene Name
ASIC2
Uniprot ID
Q16515
Uniprot Name
Acid-sensing ion channel 2
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...
Gene Name
ASIC1
Uniprot ID
P78348
Uniprot Name
Acid-sensing ion channel 1
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 gr...
Gene Name
SLC9A1
Uniprot ID
P19634
Uniprot Name
Sodium/hydrogen exchanger 1
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
Uniprot Name
Urokinase-type plasminogen activator
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, tum...
Gene Name
AOC1
Uniprot ID
P19801
Uniprot Name
Amiloride-sensitive amine oxidase [copper-containing]
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, tum...
Gene Name
AOC1
Uniprot ID
Q9TRC7
Uniprot Name
Amiloride-sensitive amine oxidase [copper-containing]
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, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
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-methylnico...
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
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...
Gene Name
SLC22A4
Uniprot ID
Q9H015
Uniprot Name
Solute carrier family 22 member 4
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]

Drug created on June 13, 2005 07:24 / Updated on November 18, 2018 04:59