All FDA-approved EMA-approved PMDA-approved
Target Card Uniprot Example: P23975

amiloride 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definition	Drug id	CAS RN
epithelial sodium channel (ENaC) inhibitors, amiloride derivatives	158	2609-46-3

Description:

Molecule

Description

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:

Dose	Unit	Route
10	mg	O

ADMET properties:

Property	Value	Reference
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 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	50 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Predicted pharmacokinetic/toxicological properties (PK-AZ):

Property	Description	Value	Unit	Confidence	Similarity
azlogd74	LogD at pH 7.4	-0.714		High	1
caco2-efflux	Caco-2 efflux ratio (BA/AB)	1.211		High	1
caco2-intrinsic-papp	Caco-2 intrinsic apparent permeability	0.782	10^-6 cm/s	High	1
dh-clint	Dog hepatocyte intrinsic clearance	1.081	uL/min/10^6 cells	High	1
dppb	Dog plasma protein binding (% unbound)	85.790	%	High	1
fcs-ppb	Fetal calf serum protein binding (% unbound)	81.540	%	High	1
herg	hERG pIC50	4.092	pIC50	High	1
hh-clint	Human hepatocyte intrinsic clearance	2.291	uL/min/10^6 cells	High	1
hlm-clint	Human liver microsomal intrinsic clearance	3.112	uL/min/mg protein	High	1
hppb	Human plasma protein binding (% unbound)	63.580	%	High	1
kinase-safety-class	ACVR2A,ACVR2B,AKT3,AURKA,AXL,BRAF,CAMK2D,CDK5,CDK9,DDR1,DYRK1B,EIF2AK3,ERBB2,FLT3,GRK2,ITK,MAP3K14,MAP3K21,MAP4K1,MAPK10,MAPK7,MTOR,NTRK1,NTRK2,PDK1,PDK2,PDK4,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PRKCD,PRKDC,SIK2,SIK3,STK33,TEK,UHMK1	38
kinase-selectivity-class	ACVR2A,ACVR2B,DYRK1B,EIF2AK3,GRK2,MAP2K3,MAP3K21,MAPK7,PIK3CD,PIK3CG,SIK2,UHMK1	12
mdck-mdr1-bcrp-efflux	MDCK-MDR1-BCRP efflux ratio	3.846		High	1
mdck-mdr1-efflux	MDCK-MDR1 efflux ratio	1.072		High	1
mh-clint	Mouse hepatocyte intrinsic clearance	3.459		High	1
mppb	Mouse plasma protein binding (% unbound)	85.140		High	1
nih-mdck-mdr1-efflux	NIH MDCK-MDR1 efflux ratio	1.991		High	1
pfas-class	PFAS structural alert (1 = True, 0 = False)	0
pppb	Pig plasma protein binding (% unbound)	89.200	%	High	1
rat-kpuu-brain	Rat brain Kpuu	0.079	%	High	1
rh-clint	Rat hepatocyte intrinsic clearance	1.581	uL/min/10^6 cells	High	1
rh-fuinc	Rat hepatocyte fraction unbound in incubation	93.400	%	High	1
rppb	Rat plasma protein binding (% unbound)	73.990	%	High	1
solubility-dd	Solubility at pH 7.4 in DMSO	901.571	uM	High	1

Approvals:

Date	Agency	Company	Orphan
Oct. 5, 1981	FDA	PADDOCK LLC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Hyperkalaemia	69.46	19.10	41	4136	64923	90559347
Hypokalaemia	64.07	19.10	51	4126	131065	90493205
Acute kidney injury	44.92	19.10	64	4113	320323	90303947
Hypomagnesaemia	39.43	19.10	23	4154	35565	90588705
Corneal abrasion	36.07	19.10	9	4168	1307	90622963
Neurological symptom	35.67	19.10	13	4164	6834	90617436
Hyponatraemia	35.64	19.10	37	4140	133501	90490769
Granulomatous liver disease	33.72	19.10	8	4169	941	90623329
Partial seizures with secondary generalisation	27.53	19.10	6	4171	483	90623787
COVID-19	27.02	19.10	36	4141	168807	90455463
Pyroglutamic acidosis	26.50	19.10	7	4170	1273	90622997
Drug interaction	25.93	19.10	46	4131	276407	90347863
Ataxia	23.59	19.10	13	4164	18029	90606241
Gingival oedema	23.19	19.10	4	4173	93	90624177
Disinhibition	22.87	19.10	6	4171	1062	90623208
Metabolic acidosis	21.64	19.10	19	4158	55657	90568613
Chills	20.89	19.10	28	4149	131953	90492317
Leukoencephalopathy	20.82	19.10	8	4169	4865	90619405
Antidiuretic hormone abnormality	19.67	19.10	3	4174	31	90624239
Depressed mood	19.24	19.10	17	4160	50205	90574065
Hydroxyprolinuria	19.11	19.10	3	4174	38	90624232

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Interstitial granulomatous dermatitis	51.20	22.11	9	2199	208	42618919
Intestinal transit time decreased	43.27	22.11	7	2201	96	42619031
Quality of life decreased	41.17	22.11	14	2194	5362	42613765
Hyperkalaemia	39.64	22.11	33	2175	80425	42538702
Varicella	31.02	22.11	9	2199	2056	42617071
Peripheral swelling	30.58	22.11	30	2178	90240	42528887
Dyskinesia oesophageal	25.14	22.11	4	2204	49	42619078
Hepatic encephalopathy	23.32	22.11	13	2195	16429	42602698
Hypokalaemia	22.73	22.11	23	2185	71698	42547429
Acute kidney injury	22.70	22.11	55	2153	367282	42251845
Mania	22.60	22.11	11	2197	10536	42608591
Diffuse alopecia	22.23	22.11	4	2204	106	42619021

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Hyperkalaemia	120.18	18.14	80	5792	135716	110447711
Hypokalaemia	80.43	18.14	71	5801	182377	110401050
Acute kidney injury	60.33	18.14	115	5757	635315	109948112
Interstitial granulomatous dermatitis	48.24	18.14	9	5863	285	110583142
Hyponatraemia	44.10	18.14	56	5816	217597	110365830
Intestinal transit time decreased	41.41	18.14	7	5865	124	110583303
Hypomagnesaemia	38.13	18.14	29	5843	60341	110523086
Corneal abrasion	34.19	18.14	9	5863	1400	110582027
Quality of life decreased	27.70	18.14	14	5858	14155	110569272
Varicella	25.49	18.14	9	5863	3746	110579681
Dyskinesia oesophageal	24.55	18.14	4	5868	56	110583371
Granulomatous liver disease	24.04	18.14	7	5865	1577	110581850
Drug level increased	23.88	18.14	20	5852	47699	110535728
Partial seizures with secondary generalisation	23.33	18.14	6	5866	853	110582574
Pyroglutamic acidosis	22.20	18.14	7	5865	2061	110581366
COVID-19	21.49	18.14	43	5829	245017	110338410
Blood creatinine increased	20.94	18.14	36	5836	182853	110400574
Drug interaction	20.77	18.14	66	5806	500117	110083310
Azotaemia	19.82	18.14	10	5862	10075	110573352
Neuromyopathy	19.01	18.14	6	5866	1773	110581654
Hepatic encephalopathy	18.78	18.14	14	5858	28242	110555185
Neurological symptom	18.28	18.14	11	5861	15597	110567830

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
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	diuretic
CHEBI has role	CHEBI:35554	cardiovascular drug
CHEBI has role	CHEBI:35674	antihypertensive agent
CHEBI has role	CHEBI:35705	immunosuppressive agent
CHEBI has role	CHEBI:38633	sodium channel blocker
MeSH PA	D004232	Diuretics
MeSH PA	D026941	Sodium Channel Blockers
MeSH PA	D045283	Natriuretic Agents
MeSH PA	D049990	Membrane Transport Modulators
MeSH PA	D062646	Acid Sensing Ion Channel Blockers
MeSH PA	D062686	Epithelial Sodium Channel Blockers

Related Drugs by ATC class:

C03DB Other potassium-sparing agents 1 drug

triamterene

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
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

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (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:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Amiloride-sensitive sodium channel, ENaC	Ion channel	P37088 P51168 P51170	SCNNA_HUMAN SCNNB_HUMAN SCNNG_HUMAN	BLOCKER	IC50	6.70		CHEMBL	CHEMBL
Urokinase-type plasminogen activator	Enzyme	P00749	UROK_HUMAN		Ki	5.16		WOMBAT-PK
Adenosine receptor A2a	GPCR	P29274	AA2AR_HUMAN		Ki	5.48		WOMBAT-PK
Amine oxidase [flavin-containing] A	Enzyme	P21397	AOFA_HUMAN		IC50	5.41		DRUG MATRIX
Sodium/hydrogen exchanger 1	Transporter	P19634	SL9A1_HUMAN		IC50	4.22		CHEMBL
Solute carrier family 22 member 1	Transporter	O15245	S22A1_HUMAN		IC50	4.24		CHEMBL
Acid-sensing ion channel 2	Ion channel	Q16515	ASIC2_HUMAN	BLOCKER	IC50	4.60		IUPHAR
Acid-sensing ion channel 1	Ion channel	P78348	ASIC1_HUMAN		IC50	5		CHEMBL
Acid-sensing ion channel 3	Ion channel	Q9UHC3	ASIC3_HUMAN		IC50	5.36		CHEMBL
Sodium/hydrogen exchanger 5	Transporter	Q14940	SL9A5_HUMAN	INHIBITOR	Ki	4.68		IUPHAR
Alpha-ketoglutarate-dependent dioxygenase FTO	Enzyme	Q9C0B1	FTO_HUMAN		IC50	5.32		CHEMBL
Amiloride-sensitive sodium channel subunit alpha	Ion channel	P37088	SCNNA_HUMAN		IC50	6.11		CHEMBL
Membrane primary amine oxidase	Enzyme		AOC3_RAT		Ki	5		CHEMBL
Sodium/hydrogen exchanger	Transporter		Q9W6Q1_9SALA		IC50	4.01		CHEMBL
Sodium/hydrogen exchanger 1	Transporter		SL9A1_RAT	INHIBITOR	Ki	6		IUPHAR
Sodium/hydrogen exchanger 2	Transporter		SL9A2_RABIT		Ki	6		CHEMBL
Urokinase-type plasminogen activator	Enzyme		UROK_MOUSE		Ki	5.64		CHEMBL
Acid-sensing ion channel 1	Ion channel		ASIC1_RAT		IC50	4.52		CHEMBL

External reference:

ID	Source
4019603	VUID
N0000147699	NUI
D00649	KEGG_DRUG
17440-83-4	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
2421	IUPHAR_LIGAND_ID
2352	INN_ID
2016-88-8	SECONDARY_CAS_RN
7DZO8EB0Z3	UNII
2658	MMSL
4166	MMSL
4167	MMSL
71823	MMSL
d00169	MMSL
4017935	VANDF
4019603	VANDF
002316	NDDF
004861	NDDF
1268944002	SNOMEDCT_US
387503008	SNOMEDCT_US
387516008	SNOMEDCT_US
412082007	SNOMEDCT_US
87395005	SNOMEDCT_US
7DZO8EB0Z3	INXIGHT DRUGS

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Amiloride Hydrochloride and Hydrochlorothiazide	HUMAN PRESCRIPTION DRUG LABEL	2	0555-0483	TABLET	5 mg	ORAL	ANDA	17 sections
amiloride hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0574-0292	TABLET	5 mg	ORAL	NDA authorized generic	20 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	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	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