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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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Amilorida [INN-Spanish]
Amiloride HCL
Amiloride hydrochloride
Amiloride hydrochloride hydrate
Amiloridum [INN-Latin]
Amyloride
Salts Not Available
Brand names
Name Company
Amipramidin
Amipramizid
Amipramizide
Amiprazidine
Guanamprazin
Guanamprazine
Midamor
Brand mixtures
Brand Name Ingredients
Alti-Amiloride HCTZ Amiloride Hcl + Hydrochlorothiazide
Ami-Hydro Tab Amiloride Hcl + Hydrochlorothiazide
Apo-Amilzide Tab Amiloride Hcl + Hydrochlorothiazide
Gen-Amilazide Amiloride Hcl + Hydrochlorothiazide
Moduret Amiloride Hcl + Hydrochlorothiazide
Novamilor Tab USP Amiloride Hcl + Hydrochlorothiazide
Nu-Amilzide 5/50 mg Tab Amiloride Hcl + Hydrochlorothiazide
Riva-Amilzide 5/50 mg Amiloride Hcl + Hydrochlorothiazide
Categories
  • Sodium channel blockers
  • Diuretics
CAS number 2016-88-8
Weight Average: 229.627
Monoisotopic: 229.04788562
Chemical Formula C6H8ClN7O
InChI Key InChIKey=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)
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Pyrazines
Substructures
  • Amino Ketones
  • Aliphatic and Aryl Amines
  • Aryl Halides
  • Pyrazines
  • Heterocyclic compounds
  • Guanidines
  • Aromatic compounds
  • Carboxamidines
  • Carboxamides and Derivatives
  • Imines
Pharmacology
Indication For use as adjunctive treatment with thiazide diuretics or other kaliuretic-diuretic agents in congestive heart failure or hypertension.
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.
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
Pathway Name SMPDB ID
Smp00133 Amiloride Pathway SMP00133
Pharmacoeconomics
Manufacturers
  • Par pharmaceutical inc
  • Sigmapharm laboratories llc
  • Paddock laboratories inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Amiloride hcl powder 5.6 USD g
Amiloride hcl 5 mg tablet 1.49 USD tablet
Midamor 5 mg tablet 1.19 USD tablet
Apo-Amiloride 5 mg Tablet 0.28 USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 240 °C Not Available
water solubility Slightly soluble Not Available
logP -0.3 Not Available
pKa 8.7 Not Available
Predicted Properties
Property Value Source
water solubility 1.22e+00 g/l ALOGPS
logP -0.72 ALOGPS
logP -0.89 ChemAxon
logS -2.3 ALOGPS
pKa (strongest acidic) 16.46 ChemAxon
pKa (strongest basic) 3.29 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 8 ChemAxon
hydrogen donor count 4 ChemAxon
polar surface area 159.29 ChemAxon
rotatable bond count 1 ChemAxon
refractivity 56.69 ChemAxon
polarizability 19.99 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C06821 Link_out
PubChem Compound 16231 Link_out
PubChem Substance 46508156 Link_out
ChemSpider 15403 Link_out
BindingDB 16173 Link_out
ChEBI 2639 Link_out
ChEMBL 2639 Link_out
Therapeutic Targets Database DAP000187 Link_out
PharmGKB PA448368 Link_out
IUPHAR 2421 Link_out
Guide to Pharmacology 2421 Link_out
HET AMR Link_out
Drug Product Database 2249510 Link_out
RxList http://www.rxlist.com/cgi/generic2/amilor.htm Link_out
Drugs.com http://www.drugs.com/cdi/amiloride.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/mod1272.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Amiloride Link_out
ATC Codes
  • C03DB01
AHFS Codes
  • 40:28.16
PDB Entries
FDA label show (377 KB)
MSDS show (39.3 KB)
Interactions
Drug Interactions
Drug Interaction
Benazepril Increased risk of hyperkalemia
Candesartan Increased risk of hyperkalemia
Captopril Increased risk of hyperkalemia
Cilazapril Increased risk of hyperkalemia
Dihydroquinidine barbiturate Decreases the antiarrhythmic effect of quinidine
Enalapril Increased risk of hyperkalemia
Eplerenone Increased risk of hyperkalemia. Monitor serum potassium levels during concomitant threapy.
Eprosartan Increased risk of hyperkalemia
Forasartan Increased risk of hyperkalemia
Fosinopril Increased risk of hyperkalemia
Irbesartan Increased risk of hyperkalemia
Lisinopril Increased risk of hyperkalemia
Losartan Increased risk of hyperkalemia
Moexipril Increased risk of hyperkalemia
Perindopril Increased risk of hyperkalemia
Polystyrene sulfonate Risk of alkalosis in renal impairment
Potassium Increased risk of hyperkalemia
Quinapril Increased risk of hyperkalemia
Quinidine Amiloride may decrease the therapeutic effect of quinidine. Monitor for changes in the therapeutic and adverse effects of quinidine if amiloride if initiated, discontinued or dose changed.
Quinidine barbiturate Decreases the antiarrhythmic effect of quinidine
Ramipril Increased risk of hyperkalemia
Saprisartan Increased risk of hyperkalemia
Spirapril Increased risk of hyperkalemia
Tasosartan Increased risk of hyperkalemia
Telmisartan Telmisartan may increase the hyperkalemic effect of Amiloride. Monitor for increased serum potassium concentrations during concomitant therapy.
Trandolapril Increased risk of hyperkalemia. Monitor serum potassium levels.
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Valsartan Increased risk of hyperkalemia
Food Interactions
  • Avoid drastic changes in dietary habit.
  • Avoid natural licorice.
  • Avoid salt substitutes containing potassium.
  • Take with food to reduce irritation.
Targets

1. Amiloride-sensitive sodium channel subunit alpha

Pharmacological action: yes
Actions: inhibitor

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

Organism class: human
UniProt ID: P37088 Link_out
Gene: SCNN1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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):457-466. Epub 2007 Jun 7. Pubmed
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Amiloride-sensitive sodium channel subunit beta

Pharmacological action: yes
Actions: inhibitor

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

Organism class: human
UniProt ID: P51168 Link_out
Gene: SCNN1B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  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
  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

3. Amiloride-sensitive sodium channel subunit gamma

Pharmacological action: yes
Actions: inhibitor

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

Organism class: human
UniProt ID: P51170 Link_out
Gene: SCNN1G Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  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
  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

4. Amiloride-sensitive sodium channel subunit delta

Pharmacological action: yes
Actions: inhibitor

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

Organism class: human
UniProt ID: P51172 Link_out
Gene: SCNN1D Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  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
  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

5. Amiloride-sensitive amine oxidase [copper-containing]

Pharmacological action: unknown
Actions: inhibitor

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

Organism class: human
UniProt ID: P19801 Link_out
Gene: ABP1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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

6. Amiloride-sensitive cation channel 1, neuronal

Pharmacological action: unknown
Actions: inhibitor

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

Organism class: human
UniProt ID: Q16515 Link_out
Gene: ACCN1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  3. Ugawa S: Identification of sour-taste receptor genes. Anat Sci Int. 2003 Dec;78(4):205-10. Pubmed
  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
  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

7. Amiloride-sensitive cation channel 2, neuronal

Pharmacological action: unknown
Actions: inhibitor

Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. Also permeable for Ca(2+), Li(+) and K(+). Generates a biphasic current with a fast inactivating and a slow sustained phase. Mediates glutamate-independent Ca(2+) entry into neurons upon acidosis. This Ca(2+) overloading is toxic for cortical neurons and may be in part responsible for ischemic brain injury. Heteromeric channel assembly seems to modulate channel properties

Organism class: human
UniProt ID: P78348 Link_out
Gene: ACCN2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  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
  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

8. Sodium/hydrogen exchanger 1

Pharmacological action: unknown
Actions: inhibitor

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

Organism class: human
UniProt ID: P19634 Link_out
Gene: SLC9A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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(-) salvage across the luminal membrane of the main pancreatic duct. J Clin Invest. 2000 Jun;105(11):1651-8. Pubmed
  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
  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
  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
  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

9. Urokinase-type plasminogen activator

Pharmacological action: unknown
Actions: inhibitor

Specifically cleave the zymogen plasminogen to form the active enzyme plasmin

Organism class: human
UniProt ID: P00749 Link_out
Gene: PLAU Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  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
  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
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
Enzymes

1. Amiloride-sensitive amine oxidase [copper-containing]

Actions: inhibitor

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

UniProt ID: P19801 Link_out
Gene: ABP1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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

2. Amiloride-sensitive amine oxidase [copper-containing]

Actions: inhibitor
UniProt ID: Q9TRC7 Link_out
Gene: ABP1
SNPs: SNPJam Report Link_out

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
  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
Transporters

1. Solute carrier family 22 member 2

Actions: inhibitor

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-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity

UniProt ID: O15244 Link_out
Gene: SLC22A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

2. Solute carrier family 22 member 1

Actions: inhibitor

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, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin- dependent kinase II and LCK tyrosine kinase

UniProt ID: O15245 Link_out
Gene: SLC22A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

3. Organic cation/carnitine transporter 1

Actions: inhibitor

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)

UniProt ID: Q9H015 Link_out
Gene: SLC22A4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19