Torasemide

Identification

Summary

Torasemide is a diuretic used to treat hypertension and edema associated with heart failure, renal failure, or liver disease.

Brand Names
Demadex, Soaanz
Generic Name
Torasemide
DrugBank Accession Number
DB00214
Background

Torasemide is a high-ceiling loop diuretic.1 Structurally, it is a pyridine-sulfonylurea used as an antihypertensive agent.4 Torasemide was first approved for clinical use by the FDA in 1993.12

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 348.42
Monoisotopic: 348.125611216
Chemical Formula
C16H20N4O3S
Synonyms
  • 1-Isopropyl-3-((4-m-toluidino-3-pyridyl)sulfonyl)urea
  • N-(((1-Methylethyl)amino)carbonyl)-4-((3-methylphenyl)amino)-3-pyridinesulfonamide
  • Torasemida
  • Torasemide
  • Torasémide
  • Torasemidum
  • Torsemide
External IDs
  • AC-4464
  • AC4464
  • BM-02.015
  • BM-02015
  • BM02.015

Pharmacology

Indication

Torasemide is indicated for the treatment of edema associated with congestive heart failure, renal or hepatic diseases. From this condition, it has been observed that torasemide is very effective in cases of kidney failure.Label

As well, torasemide is approved to be used as an antihypertensive agent either alone or in combination with other antihypertensives.Label

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofEdema•••••••••••••••••••••••
Management ofEdema•••••••••••••••••••••••
Management ofEdema•••••••••••••••••••••••
Management ofHypertension•••••••••••••••••••••• ••••••••• ••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

It is widely known that administration of torasemide can attenuate renal injury and reduce the severity of acute renal failure. This effect is obtained by increasing urine output and hence, facilitating fluid, acid-base and potassium control.2 This effect is obtained by the increase in the excretion of urinary sodium and chloride.3

Several reports have indicated that torasemide presents a long-lasting diuresis and less potassium excretion which can be explained by the effect that torasemide has on the renin-angiotensin-aldosterone system. This effect is very similar to the effect observed with the administration of combination therapy with furosemide and spironolactone and it is characterized by a decrease in plasma brain natriuretic peptide and improved measurements of left ventricular function.3

Above the aforementioned effect, torasemide presents a dual effect .in which the inhibition of aldosterone which donates torasemide with a potassium-sparing action.2

Torasemide has been shown to reduce extracellular fluid volume and blood pressure in hypertensive patients suffering from chronic kidney disease. As well, some reports have indicated that torasemide can reduce myocardial fibrosis by reducing the collagen accumulation. This effect is suggested to be related to the decrease in aldosterone which in order has been shown to reduce the production of the enzyme procollagen type I carboxy-terminal proteinase which is known to be overexpressed in heart failure patients.1

Mechanism of action

As mentioned above, torasemide is part of the loop diuretics and thus, it acts by reducing the oxygen demand in the medullary thick ascending loop of Henle by inhibiting the Na+/K+/Cl- pump on the luminal cell membrane surface.2 This action is obtained by the binding of torasemide to a chloride ion-binding site of the transport molecule.12

Torasemide is known to have an effect in the renin-angiotensin-aldosterone system by inhibiting the downstream cascade after the activation of angiotensin II. This inhibition will produce a secondary effect marked by the reduction of the expression of aldosterone synthase, TGF-B1 and thromboxane A2 and a reduction on the aldosterone receptor binding.2,3

TargetActionsOrganism
ASolute carrier family 12 member 2
inhibitor
Humans
ASolute carrier family 12 member 1
inhibitor
Humans
Absorption

Torasemide is the diuretic with the highest oral bioavailability even in advanced stages of chronic kidney disease.1 This bioavailability tends to be higher than 80% regardless of the patient condition. The maximal serum concentration is reported to be of 1 hour and the absorption parameters are not affected by its use concomitantly with food.3

Volume of distribution

The volume of distribution of torasemide is 0.2 L/kg.5

Protein binding

Torasemide is found to be highly bound to plasma proteins, representing over 99% of the administered dose.5

Metabolism

Torasemide is extensively metabolized in the liver and only 20% of the dose remains unchanged and it is recovered in the urine.5 Metabolized via the hepatic CYP2C8 and CYP2C9 mainly by reactions of hydroxylation, oxidation and reduction to 5 metabolites.7 The major metabolite, M5, is pharmacologically inactive. There are 2 minor metabolites, M1, possessing one-tenth the activity of torasemide, and M3, equal in activity to torasemide. Overall, torasemide appears to account for 80% of the total diuretic activity, while metabolites M1 and M3 account for 9% and 11%, respectively.6

Hover over products below to view reaction partners

Route of elimination

Torasemide is mainly hepatically processed and excreted in the feces from which about 70-80% of the administered dose is excreted by this pathway. On the other hand, about 20-30% of the administered dose is found in the urine.12

Half-life

The average half-life of torasemide is 3.5 hours.3

Clearance

The clearance rate of torasemide is considerably reduced by the presence of renal disorders.5

Adverse Effects
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Toxicity

The oral LD50 of torasemide in the rat is 5 g/kg. When overdose occurs, there is a marked diuresis with the danger of loss of fluid and electrolytes which has been seen to lead to somnolence, confusion, hypotension, hyponatremia, hypokalemia, hypochloremic alkalosis, hemoconcentration dehydration and circulatory collapse. This effects can include some gastrointestinal disturbances.13

There is no increase in tumor incidence with torasemide and it is proven to not be mutagenic, not fetotoxic or teratogenic.Label

Pathways
PathwayCategory
Torsemide Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirTorasemide may increase the excretion rate of Abacavir which could result in a lower serum level and potentially a reduction in efficacy.
AbaloparatideThe risk or severity of adverse effects can be increased when Torasemide is combined with Abaloparatide.
AbataceptThe metabolism of Torasemide can be increased when combined with Abatacept.
AbirateroneThe metabolism of Torasemide can be decreased when combined with Abiraterone.
AbrocitinibThe metabolism of Abrocitinib can be decreased when combined with Torasemide.
Food Interactions
  • Take with or without food. Food delays the Cmax by 30 minutes but does not impact efficacy.

Products

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Product Images
International/Other Brands
Britomar (Ferrer) / Diuver (Pliva) / Examide (Apex) / Luprac (Tanabe Mitshubishi Pharma) / Soaanz (Sarfez Pharmaceuticals) / Torem (Berlin-Chemie) / Trifas (Meranini)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
DemadexTablet100 mg/1OralMEDA Pharmaceuticals2015-01-012020-07-31US flag
DemadexTablet5 mg/1OralMeda Pharmaceuticals Inc.2015-01-012014-12-19US flag
DemadexTablet10 mg/1OralMeda Pharmaceuticals Inc.2009-02-202009-08-04US flag
DemadexTablet20 mg/1OralPhysicians Total Care, Inc.2009-10-21Not applicableUS flag
DemadexTablet100 mg/1OralRoche Pharmaceuticals2007-02-06Not applicableUS flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
TorsemideTablet20 mg/1OralApotex Corp.2005-06-062017-09-01US flag
TorsemideTablet100 mg/1OralAurobindo Pharma Limited2007-10-17Not applicableUS flag
TorsemideTablet20 mg/1OralCarilion Materials Management2011-01-01Not applicableUS flag
TorsemideTablet10 mg/1OralXLCARE Pharmaceuticals INC.2024-09-10Not applicableUS flag
TorsemideTablet20 mg/1OralHikma Pharmaceuticals USA Inc.2005-03-03Not applicableUS flag

Categories

ATC Codes
C03CA04 — TorasemideG01AE10 — Combinations of sulfonamides
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as pyridinesulfonamides. These are heterocyclic compounds containing a pyridine ring substituted by one or more sulfonamide groups.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyridines and derivatives
Sub Class
Pyridinesulfonamides
Direct Parent
Pyridinesulfonamides
Alternative Parents
Toluenes / Sulfonylureas / Dihydropyridines / Secondary ketimines / Organosulfonic acids and derivatives / Heteroaromatic compounds / Aminosulfonyl compounds / Propargyl-type 1,3-dipolar organic compounds / Carboximidic acids and derivatives / Azacyclic compounds
show 4 more
Substituents
Aminosulfonyl compound / Aromatic heteromonocyclic compound / Azacycle / Benzenoid / Carboximidic acid derivative / Dihydropyridine / Heteroaromatic compound / Hydrocarbon derivative / Hydropyridine / Monocyclic benzene moiety
show 16 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
secondary amino compound, aminopyridine, N-sulfonylurea (CHEBI:9637)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
W31X2H97FB
CAS number
56211-40-6
InChI Key
NGBFQHCMQULJNZ-UHFFFAOYSA-N
InChI
InChI=1S/C16H20N4O3S/c1-11(2)18-16(21)20-24(22,23)15-10-17-8-7-14(15)19-13-6-4-5-12(3)9-13/h4-11H,1-3H3,(H,17,19)(H2,18,20,21)
IUPAC Name
1-({4-[(3-methylphenyl)amino]pyridin-3-yl}sulfonyl)-3-(propan-2-yl)urea
SMILES
CC(C)NC(=O)NS(=O)(=O)C1=C(NC2=CC=CC(C)=C2)C=CN=C1

References

Synthesis Reference

Fritz Topfmeier, Gustav Lettenbauer, "Process for the preparation of a stable modification of torasemide." U.S. Patent USRE0345806, issued June, 1975.

USRE0345806
General References
  1. Lopez B, Gonzalez A, Hermida N, Laviades C, Diez J: Myocardial fibrosis in chronic kidney disease: potential benefits of torasemide. Kidney Int Suppl. 2008 Dec;(111):S19-23. doi: 10.1038/ki.2008.512. [Article]
  2. Li XM, Jin DX, Cong HL: Could torasemide be a prophylactic agent of contrast induced acute kidney injury? A review about this field. Eur Rev Med Pharmacol Sci. 2013 Jul;17(14):1845-9. [Article]
  3. Buggey J, Mentz RJ, Pitt B, Eisenstein EL, Anstrom KJ, Velazquez EJ, O'Connor CM: A reappraisal of loop diuretic choice in heart failure patients. Am Heart J. 2015 Mar;169(3):323-33. doi: 10.1016/j.ahj.2014.12.009. Epub 2015 Jan 6. [Article]
  4. Dunn CJ, Fitton A, Brogden RN: Torasemide. An update of its pharmacological properties and therapeutic efficacy. Drugs. 1995 Jan;49(1):121-42. [Article]
  5. Knauf H, Mutschler E: Clinical pharmacokinetics and pharmacodynamics of torasemide. Clin Pharmacokinet. 1998 Jan;34(1):1-24. doi: 10.2165/00003088-199834010-00001. [Article]
  6. Neugebauer G, Besenfelder E, von Mollendorff E: Pharmacokinetics and metabolism of torasemide in man. Arzneimittelforschung. 1988 Jan;38(1A):164-6. [Article]
  7. Barroso MB, Alonso RM, Jimenez RM: Simultaneous determination of torasemide and its major metabolite M5 in human urine by high-performance liquid chromatography-electrochemical detection. J Chromatogr Sci. 2001 Nov;39(11):491-6. [Article]
  8. Coleman J., Cox A. and Cowley N. (2011). Side Effects of Drugs Annual. Elsevier.
  9. FDA approvals [Link]
  10. Cleveland Clinic [Link]
  11. Hypertension Canada [Link]
  12. Indian Journal of Clinical Practice [Link]
  13. EMC [Link]
  14. FDA Approved Drug Products: Soaanz (torsemide) tablets for oral use [Link]
  15. Demadex (Torsemide) FDA Label [Link]
Human Metabolome Database
HMDB0014359
KEGG Drug
D00382
PubChem Compound
41781
PubChem Substance
46504760
ChemSpider
38123
BindingDB
64107
RxNav
38413
ChEBI
9637
ChEMBL
CHEMBL1148
ZINC
ZINC000000005823
Therapeutic Targets Database
DAP000745
PharmGKB
PA451733
RxList
RxList Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Torasemide
FDA label
Download (92.4 KB)
MSDS
Download (74.7 KB)

Clinical Trials

Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
Not AvailableCompletedNot AvailableCoronavirus Disease 2019 (COVID‑19) / COVID / Hypertension1somestatusstop reasonjust information to hide
Not AvailableCompletedTreatmentEdema2somestatusstop reasonjust information to hide
Not AvailableRecruitingNot AvailableCongenital Mitral Insufficiency2somestatusstop reasonjust information to hide
Not AvailableRecruitingNot AvailableHeart Failure Congenital1somestatusstop reasonjust information to hide
Not AvailableRecruitingTreatmentAcute Decompensated Heart Failure (ADHF)1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
  • Hoffmann la roche inc
  • Bedford laboratories
  • Luitpold pharmaceuticals inc
  • Meda pharmaceuticals inc
  • Apotex inc etobicoke site
  • Aurobindo pharma ltd
  • Hetero drugs ltd
  • Par pharmaceutical inc
  • Pliva pharmaceutical industry inc
  • Roxane laboratories inc
  • Sun pharmaceutical industries ltd
  • Teva pharmaceuticals usa inc
Packagers
  • American Regent
  • Apotex Inc.
  • Aurobindo Pharma Ltd.
  • Camber Pharmaceuticals Inc.
  • Cardinal Health
  • Diversified Healthcare Services Inc.
  • F Hoffmann-La Roche Ltd.
  • General Injectables and Vaccines Inc.
  • Greenstone LLC
  • Heartland Repack Services LLC
  • Hetero Drugs Ltd.
  • Ivax Pharmaceuticals
  • Mckesson Corp.
  • Meda AB
  • Murfreesboro Pharmaceutical Nursing Supply
  • Neuman Distributors Inc.
  • Palmetto Pharmaceuticals Inc.
  • Par Pharmaceuticals
  • Physicians Total Care Inc.
  • Pliva Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepak Systems Inc.
  • Resource Optimization and Innovation LLC
  • Roxane Labs
  • Sun Pharmaceutical Industries Ltd.
  • Teva Pharmaceutical Industries Ltd.
  • UDL Laboratories
  • Vangard Labs Inc.
Dosage Forms
FormRouteStrength
Injection, solutionIntravenous10 mg/1mL
TabletOral10 mg/1
TabletOral100 mg/1
TabletOral20 mg/1
TabletOral5 mg/1
LiquidIntravenous10 mg / mL
TabletOral100 mg
TabletOral20 mg
TabletOral5 mg
Injection, solutionIntravenous10 mg/2ml
Injection, solutionIntravenous200 mg/20ml
SolutionIntravenous10 mg/2ml
Tablet, film coatedOral20 mg/1
Tablet, film coatedOral40 mg/1
Tablet, film coatedOral60 mg/1
Tablet, extended releaseOral
Tablet, extended releaseOral10 mg
Tablet, extended releaseOral5 mg
Injection, suspensionIntravenous10 MG/2ML
TabletOral2.5 MG
TabletOral200 MG
TabletOral
TabletOral50 MG
TabletOral10 mg
Prices
Unit descriptionCostUnit
Demadex 100 mg tablet5.69USD tablet
Torsemide 100 mg tablet3.16USD tablet
Demadex 20 mg tablet1.59USD tablet
Demadex 10 mg tablet1.39USD tablet
Demadex 5 mg tablet1.28USD tablet
Torsemide 20 mg tablet0.85USD tablet
Torsemide 10 mg tablet0.73USD tablet
Torsemide 5 mg tablet0.66USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US10154963No2018-12-182033-10-06US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)163-164 °C'MSDS'
water solubilitySoluble'MSDS'
logP3.356'MSDS'
pKa7.1'FDA label'
Predicted Properties
PropertyValueSource
Water Solubility0.0596 mg/mLALOGPS
logP1.76ALOGPS
logP1.86Chemaxon
logS-3.8ALOGPS
pKa (Strongest Acidic)5.92Chemaxon
pKa (Strongest Basic)4.2Chemaxon
Physiological Charge-1Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count3Chemaxon
Polar Surface Area100.19 Å2Chemaxon
Rotatable Bond Count4Chemaxon
Refractivity91.89 m3·mol-1Chemaxon
Polarizability36.15 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9156
Blood Brain Barrier+0.6871
Caco-2 permeable-0.5374
P-glycoprotein substrateNon-substrate0.799
P-glycoprotein inhibitor INon-inhibitor0.7695
P-glycoprotein inhibitor IINon-inhibitor0.8232
Renal organic cation transporterNon-inhibitor0.9185
CYP450 2C9 substrateSubstrate0.6049
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.7558
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.6692
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorInhibitor0.5905
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6324
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.8366
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.8740 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9854
hERG inhibition (predictor II)Non-inhibitor0.8668
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-MSsplash10-001i-7922000000-38709aad9fb92fea20e1
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-03di-0090000000-bcaf4981571fb662df86
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-03di-0090000000-00cc7369c05298ea1c97
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-03di-0490000000-60171fe07a2f255596e3
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-01ot-2950000000-359d6835f9bf703a0701
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-000t-3910000000-a5ec65a6dbedfe7a30d3
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0564-6900000000-051171526b146f5d076c
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-03di-0190000000-1b2efe76058c7bf06b4a
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03di-0091000000-548edfa45514c501788d
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03di-0090000000-d7326b2b38380cd06e26
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03di-0490000000-b9f43c4768937947d77f
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-0940000000-7b7084526f7c13bf6443
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00lr-0910000000-81aa8c9ff5d9a3cd3c10
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0159-0900000000-87860a9931a8414432cf
MS/MS Spectrum - , positiveLC-MS/MSsplash10-03di-1590000000-1b7d966c20cec1451f6c
MS/MS Spectrum - , positiveLC-MS/MSsplash10-03di-0490000000-bd8b6af3fe8d0f10e117
MS/MS Spectrum - , positiveLC-MS/MSsplash10-02ai-2940000000-5beb0e7e25d393903803
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03di-0390000000-314819093d7d5a1f48f4
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0002-0090000000-8669c4785f3a6ba6312d
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-03fr-5090000000-9e9e23b73be7520cafc5
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-03e9-0490000000-c26cc5ed6e5a8fd562b6
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0002-0090000000-9d852705fe8bb0d772dc
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-2920000000-1a98d7f41932aee6e44d
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0535-1920000000-626044ee7770e352b9d5
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-193.4783449
predicted
DarkChem Lite v0.1.0
[M-H]-194.3572449
predicted
DarkChem Lite v0.1.0
[M-H]-182.6581
predicted
DeepCCS 1.0 (2019)
[M+H]+193.8189449
predicted
DarkChem Lite v0.1.0
[M+H]+195.2768449
predicted
DarkChem Lite v0.1.0
[M+H]+185.0161
predicted
DeepCCS 1.0 (2019)
[M+Na]+193.2753449
predicted
DarkChem Lite v0.1.0
[M+Na]+194.2030449
predicted
DarkChem Lite v0.1.0
[M+Na]+192.15666
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Cation-chloride cotransporter which mediates the electroneutral transport of chloride, potassium and/or sodium ions across the membrane (PubMed:16669787, PubMed:32081947, PubMed:32294086, PubMed:33597714, PubMed:7629105). Plays a vital role in the regulation of ionic balance and cell volume (PubMed:16669787, PubMed:32081947, PubMed:32294086, PubMed:7629105)
Specific Function
ammonium transmembrane transporter activity
Gene Name
SLC12A2
Uniprot ID
P55011
Uniprot Name
Solute carrier family 12 member 2
Molecular Weight
131445.825 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  2. Baumann P: Pharmacology and pharmacokinetics of citalopram and other SSRIs. Int Clin Psychopharmacol. 1996 Mar;11 Suppl 1:5-11. [Article]
  3. Hyttel J, Bogeso KP, Perregaard J, Sanchez C: The pharmacological effect of citalopram residues in the (S)-(+)-enantiomer. J Neural Transm Gen Sect. 1992;88(2):157-60. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Renal sodium, potassium and chloride ion cotransporter that mediates the transepithelial NaCl reabsorption in the thick ascending limb and plays an essential role in the urinary concentration and volume regulation (PubMed:21321328). Electrically silent transporter system (By similarity)
Specific Function
sodium
Gene Name
SLC12A1
Uniprot ID
Q13621
Uniprot Name
Solute carrier family 12 member 1
Molecular Weight
121449.13 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  2. Vormfelde SV, Sehrt D, Toliat MR, Schirmer M, Meineke I, Tzvetkov M, Nurnberg P, Brockmoller J: Genetic variation in the renal sodium transporters NKCC2, NCC, and ENaC in relation to the effects of loop diuretic drugs. Clin Pharmacol Ther. 2007 Sep;82(3):300-9. Epub 2007 Apr 25. [Article]
  3. Fortuno A, Muniz P, Ravassa S, Rodriguez JA, Fortuno MA, Zalba G, Diez J: Torasemide inhibits angiotensin II-induced vasoconstriction and intracellular calcium increase in the aorta of spontaneously hypertensive rats. Hypertension. 1999 Jul;34(1):138-43. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
Specific Function
arachidonic acid epoxygenase activity
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Miners JO, Coulter S, Birkett DJ, Goldstein JA: Torsemide metabolism by CYP2C9 variants and other human CYP2C subfamily enzymes. Pharmacogenetics. 2000 Apr;10(3):267-70. [Article]
  2. Polasek TM, Elliot DJ, Lewis BC, Miners JO: Mechanism-based inactivation of human cytochrome P4502C8 by drugs in vitro. J Pharmacol Exp Ther. 2004 Dec;311(3):996-1007. doi: 10.1124/jpet.104.071803. Epub 2004 Aug 10. [Article]
  3. Ong CE, Coulter S, Birkett DJ, Bhasker CR, Miners JO: The xenobiotic inhibitor profile of cytochrome P4502C8. Br J Clin Pharmacol. 2000 Dec;50(6):573-80. doi: 10.1046/j.1365-2125.2000.00316.x. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
Specific Function
(R)-limonene 6-monooxygenase activity
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  2. Miners JO, Coulter S, Birkett DJ, Goldstein JA: Torsemide metabolism by CYP2C9 variants and other human CYP2C subfamily enzymes. Pharmacogenetics. 2000 Apr;10(3):267-70. [Article]
  3. Flockhart Table of Drug Interactions [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
Specific Function
antioxidant activity
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Albumin
Molecular Weight
69365.94 Da
References
  1. Knauf H, Mutschler E: Clinical pharmacokinetics and pharmacodynamics of torasemide. Clin Pharmacokinet. 1998 Jan;34(1):1-24. doi: 10.2165/00003088-199834010-00001. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Mediates the Na(+)-independent uptake of organic anions (PubMed:10358072, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) (PubMed:10358072, PubMed:10601278, PubMed:10873595, PubMed:11159893, PubMed:12196548, PubMed:12568656, PubMed:15159445, PubMed:15970799, PubMed:16627748, PubMed:17412826, PubMed:19129463, PubMed:26979622). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Involved in the clearance of endogenous and exogenous substrates from the liver (PubMed:10358072, PubMed:10601278). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:10601278, PubMed:15159445, PubMed:15970799). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748). Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463)
Specific Function
bile acid transmembrane transporter activity
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Coleman J., Cox A. and Cowley N. (2011). Side Effects of Drugs Annual. Elsevier.

Drug created at June 13, 2005 13:24 / Updated at August 02, 2024 07:23