amiloride ๐Ÿถ Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
158 2609-46-3

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • amiloride
  • amiloride hydrochloride
  • amiloride hydrochloride anhydrous
  • amiloride hydrochloride dihydrate
  • amiloride HCl
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)
  • Molecular weight: 229.63
  • Formula: C6H8ClN7O
  • CLOGP: 0.41
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 5
  • TPSA: 156.79
  • ALOGS: -2.57
  • ROTB: 1

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
10 mg O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 50 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 49 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.47 ยตM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 50 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Approvals:

DateAgencyCompanyOrphan
Oct. 5, 1981 FDA PADDOCK LLC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hyperkalaemia 48.16 18.81 31 2746 48058 50554289
Hypokalaemia 47.51 18.81 39 2738 87953 50514394
Granulomatous liver disease 34.29 18.81 8 2769 735 50601612
Partial seizures with secondary generalisation 28.92 18.81 6 2771 320 50602027
Neurological symptom 27.10 18.81 10 2767 4572 50597775
Hypomagnesaemia 25.84 18.81 16 2761 23140 50579207
Hyponatraemia 24.10 18.81 28 2749 96111 50506236
Disinhibition 23.48 18.81 6 2771 804 50601543
Gingival oedema 23.27 18.81 4 2773 76 50602271
Corneal abrasion 23.11 18.81 6 2771 856 50601491
Leukoencephalopathy 21.23 18.81 8 2769 3875 50598472
Acute kidney injury 20.32 18.81 41 2736 228017 50374330
Vitamin B12 decreased 19.86 18.81 7 2770 2808 50599539
Antidiuretic hormone abnormality 19.43 18.81 3 2774 28 50602319

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Interstitial granulomatous dermatitis 52.64 24.30 9 1592 168 29572758
Hyperkalaemia 33.06 24.30 27 1574 61365 29511561
Dyskinesia oesophageal 24.68 24.30 4 1597 53 29572873

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hyperkalaemia 92.45 17.87 65 4020 101064 64393583
Interstitial granulomatous dermatitis 49.18 17.87 9 4076 213 64494434
Hypokalaemia 44.00 17.87 46 4039 121857 64372790
Hyponatraemia 36.63 17.87 46 4039 148293 64346354
Acute kidney injury 28.40 17.87 77 4008 449163 64045484
Partial seizures with secondary generalisation 25.60 17.87 6 4079 486 64494161
Hypomagnesaemia 25.09 17.87 20 4065 37356 64457291
Granulomatous liver disease 24.62 17.87 7 4078 1215 64493432
Drug level increased 24.46 17.87 19 4066 34177 64460470
Dyskinesia oesophageal 23.58 17.87 4 4081 60 64494587
Blood creatinine increased 22.81 17.87 35 4050 135747 64358900
Neurological symptom 21.80 17.87 10 4075 6854 64487793
Corneal abrasion 21.69 17.87 6 4079 942 64493705
Azotaemia 20.95 17.87 10 4075 7492 64487155
Neuromyopathy 19.52 17.87 6 4079 1362 64493285
Vitamin B12 decreased 19.12 17.87 7 4078 2708 64491939
Leukoencephalopathy 18.59 17.87 9 4076 6958 64487689

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC C03DB01 CARDIOVASCULAR SYSTEM
DIURETICS
ALDOSTERONE ANTAGONISTS AND OTHER POTASSIUM-SPARING AGENTS
Other potassium-sparing agents
FDA PE N0000008859 Decreased Renal K+ Excretion
FDA PE N0000175359 Increased Diuresis
FDA EPC N0000175418 Potassium-sparing Diuretic
CHEBI has role CHEBI:35498 diuretics
CHEBI has role CHEBI:38633 sodium channel blockers
MeSH PA D062646 Acid Sensing Ion Channel Blockers
MeSH PA D004232 Diuretics
MeSH PA D062686 Epithelial Sodium Channel Blockers
MeSH PA D049990 Membrane Transport Modulators
MeSH PA D045283 Natriuretic Agents
MeSH PA D026941 Sodium Channel Blockers

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Hypertensive disorder indication 38341003 DOID:10763
Edema indication 267038008
Hypokalemia Prevention indication
Hypercalcemia off-label use 66931009 DOID:12678
Nephrogenic diabetes insipidus off-label use 111395007 DOID:12387
Peripheral Edema due to Chronic Heart Failure off-label use
Pulmonary Edema due to Chronic Heart Failure off-label use
Anuria contraindication 2472002 DOID:2983
Hypercholesterolemia contraindication 13644009
Hyperkalemia contraindication 14140009
Secondary angle-closure glaucoma contraindication 21571006
Hypovolemia contraindication 28560003
Dehydration contraindication 34095006
Hyperuricemia contraindication 35885006 DOID:1920
Hypokalemia contraindication 43339004
Acidosis contraindication 51387008
Systemic lupus erythematosus contraindication 55464009 DOID:9074
Sympathectomy contraindication 57071006
Hyperparathyroidism contraindication 66999008 DOID:13543
Hypochloremic alkalosis contraindication 70134007
Hepatic coma contraindication 72836002 DOID:12550
Diabetes mellitus contraindication 73211009 DOID:9351
Oliguria contraindication 83128009
Hyponatremia contraindication 89627008
Gout contraindication 90560007 DOID:13189
Kidney disease contraindication 90708001 DOID:557
Diabetic renal disease contraindication 127013003
Hypomagnesemia contraindication 190855004
Acute pancreatitis contraindication 197456007 DOID:2913
Disease of liver contraindication 235856003 DOID:409
Neonatal hyperbilirubinemia contraindication 281610001
Azotemia contraindication 445009001




๐Ÿถ Veterinary Drug Use

None

๐Ÿถ Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.64 Basic
pKa2 4.41 Basic
pKa3 0.72 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Amiloride-sensitive sodium channel, ENaC Ion channel BLOCKER IC50 6.70 CHEMBL CHEMBL
Sodium/hydrogen exchanger 5 Transporter INHIBITOR Ki 4.68 IUPHAR
Amiloride-sensitive sodium channel subunit alpha Ion channel IC50 6.11 CHEMBL
Urokinase-type plasminogen activator Enzyme Ki 5.16 WOMBAT-PK
Adenosine receptor A2a GPCR Ki 5.48 WOMBAT-PK
Amine oxidase [flavin-containing] A Enzyme IC50 5.41 DRUG MATRIX
Sodium/hydrogen exchanger 1 Transporter IC50 4.22 CHEMBL
Solute carrier family 22 member 1 Transporter IC50 4.24 CHEMBL
Acid-sensing ion channel 2 Ion channel BLOCKER IC50 4.60 IUPHAR
Acid-sensing ion channel 1 Ion channel IC50 5 CHEMBL
Acid-sensing ion channel 3 Ion channel IC50 5.36 CHEMBL
Membrane primary amine oxidase Enzyme Ki 5 CHEMBL
Sodium/hydrogen exchanger 1 Transporter INHIBITOR Ki 6 IUPHAR
Sodium/hydrogen exchanger 2 Transporter Ki 6 CHEMBL
Urokinase-type plasminogen activator Enzyme Ki 5.64 CHEMBL
Sodium/hydrogen exchanger Transporter IC50 4.01 CHEMBL
Acid-sensing ion channel 1 Ion channel IC50 4.52 CHEMBL

External reference:

IDSource
4019603 VUID
N0000147699 NUI
D00649 KEGG_DRUG
17440-83-4 SECONDARY_CAS_RN
2016-88-8 SECONDARY_CAS_RN
1298837 RXNORM
C0002502 UMLSCUI
CHEBI:2639 CHEBI
AMR PDB_CHEM_ID
CHEMBL945 ChEMBL_ID
DB00594 DRUGBANK_ID
CHEMBL1398126 ChEMBL_ID
D000584 MESH_DESCRIPTOR_UI
16231 PUBCHEM_CID
2352 INN_ID
2421 IUPHAR_LIGAND_ID
7DZO8EB0Z3 UNII
2658 MMSL
4166 MMSL
4167 MMSL
71823 MMSL
d00169 MMSL
002316 NDDF
004861 NDDF
4017935 VANDF
4019603 VANDF
387503008 SNOMEDCT_US
387516008 SNOMEDCT_US
412082007 SNOMEDCT_US
87395005 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Amiloride Hydrochloride and Hydrochlorothiazide HUMAN PRESCRIPTION DRUG LABEL 2 0378-0577 TABLET 5 mg ORAL ANDA 23 sections
Amiloride Hydrochloride and Hydrochlorothiazide HUMAN PRESCRIPTION DRUG LABEL 2 0555-0483 TABLET 5 mg ORAL ANDA 17 sections
amiloride hydrocloride HUMAN PRESCRIPTION DRUG LABEL 1 0574-0292 TABLET 5 mg ORAL NDA 22 sections
Amiloride Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 42794-005 TABLET 5 mg ORAL ANDA 18 sections
Amiloride Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 49884-117 TABLET 5 mg ORAL ANDA 18 sections
Amiloride Hydrochloride and Hydrochlorothiazide HUMAN PRESCRIPTION DRUG LABEL 2 50090-0513 TABLET 5 mg ORAL ANDA 17 sections
Amiloride Hydrochloride and Hydrochlorothiazide HUMAN PRESCRIPTION DRUG LABEL 2 54868-0667 TABLET 5 mg ORAL ANDA 12 sections
AMILORIDE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 54868-5214 TABLET 5 mg ORAL NDA 22 sections
amiloride hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 57721-671 TABLET 5 mg ORAL ANDA 18 sections
Amiloride Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 60429-275 TABLET 5 mg ORAL ANDA 18 sections
Amiloride Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 60429-275 TABLET 5 mg ORAL ANDA 18 sections
Amiloride Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 63629-2114 TABLET 5 mg ORAL ANDA 18 sections
Amiloride Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 63629-2114 TABLET 5 mg ORAL ANDA 18 sections
Amiloride Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 68151-0162 TABLET 5 mg ORAL ANDA 18 sections