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Identification
Name Indapamide
Accession Number DB00808 (APRD01031)
Type small molecule
Groups approved
Description

A benzamide-sulfonamide-indole. It is called a thiazide-like diuretic but structure is different enough (lacking the thiazo-ring) so it is not clear that the mechanism is comparable. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Indapamida [INN-Spanish]
  • Indapamidum [INN-Latin]
Brand names
  • Apo-Indapamide
  • Arifon
  • Bajaten
  • Cormil
  • Fludex
  • Idapamide
  • Indamol
  • Ipamix
  • Lozide
  • Lozol
  • Natrilix
  • Natrix
  • Noranat
  • Novo-Indapamide
  • Nu-Indapamide
  • Pressurai
  • Tandix
  • Tertensif
  • Veroxil
Brand name mixtures Not Available
Categories
  • Antihypertensive Agents
  • Diuretics
CAS number 26807-65-8
Weight Average: 365.835
Monoisotopic: 365.060089790
Chemical Formula C16H16ClN3O3S
InChI Key InChIKey=NDDAHWYSQHTHNT-UHFFFAOYSA-N
InChI
InChI=1S/C16H16ClN3O3S/c1-10-8-11-4-2-3-5-14(11)20(10)19-16(21)12-6-7-13(17)15(9-12)24(18,22)23/h2-7,9-10H,8H2,1H3,(H,19,21)(H2,18,22,23)
Plain Text
IUPAC Name
4-chloro-N-(2-methyl-2,3-dihydro-1H-indol-1-yl)-3-sulfamoylbenzamide
SMILES
CC1CC2=C(C=CC=C2)N1NC(=O)C1=CC(=C(Cl)C=C1)S(N)(=O)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Indoles and Indole Derivatives
  • Benzenesulfonamides
  • Phenethylamines
  • Benzamides
  • Amphetamines
Substructures
  • Carboxylic Acids and Derivatives
  • Indoles and Indole Derivatives
  • Amino Ketones
  • Sulfonyls
  • Benzene and Derivatives
  • Aryl Halides
  • Benzenesulfonamides
  • Halobenzenes
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Sulfonamides
  • Hydrazine Derivatives
  • Benzoyl Derivatives
  • Phenylhydrazines
  • Benzamides
  • Anilines
  • Amphetamines
  • Pyrrolines
Pharmacology
Indication For the treatment of hypertension, alone or in combination with other antihypertensive drugs, as well as for the treatment of salt and fluid retention associated with congestive heart failure or edema from pregnancy (appropriate only in the management of edema of pathologic origin during pregnancy when clearly needed). Also used for the management of edema as a result of various causes.
Pharmacodynamics Indapamide is an antihypertensive and a diuretic. It contains both a polar sulfamoyl chlorobenzamide moiety and a lipid- soluble methylindoline moiety. Indapamide bears a structural similarity to the triazide diuretics which are known to decrease vascular smooth muscle reactivity. However, it differs chemically from the thiazides in that it does not possess the thiazide ring system and contains only one sulfonamide group. Indapamide appears to cause vasodilation, probably by inhibiting the passage of calcium and other ions (sodium, potassium) across membranes. This same effect may cause hypokalcemia in susceptible individuals. Indapamide has also been shown to cause uterine myometrial relaxation in experimental animals. Overall, indapamide has an extra-renal antihypertensive action resulting in a decrease in vascular hyperreactivity and a reduction in total peripheral and arteriolar resistance.
Mechanism of action Indapamide blocks the slow component of delayed rectifier potassium current (IKs) without altering the rapid component (IKr) or the inward rectifier current. Specifically it blocks or antagonizes the action the proteins KCNQ1 and KCNE1. Indapamide is also thought to stimulate the synthesis of the vasodilatory hypotensive prostaglandin PGE2.
Absorption Rapidly absorbed from gastrointestinal tract.
Volume of distribution Not Available
Protein binding 71-79%
Metabolism

Primarily hepatic. Indapamide is an extensively metabolized drug with only about 7+ACU- of the total dose administered, recovered in the urine as unchanged drug during the first 48 hours after administration.
Route of elimination Indapamide is an extensively metabolized drug, with only about 7% of the total dose administered, recovered in the urine as unchanged drug during the first 48 hours after administration.
Half life 14 hours (biphasic)
Clearance Not Available
Toxicity Side effects include electrolyte imbalance (potassium or salt depletion due to too much fluid loss), nausea, stomach disorders, vomiting, weakness
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00110 Indapamide Pathway SMP00110
Pharmacoeconomics
Manufacturers
  • Actavis elizabeth llc
  • Alphapharm party ltd
  • Cadista pharmaceuticals inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
  • Sanofi aventis us llc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Indapamide 2.5 mg tablet 0.85 USD tablet
Indapamide 1.25 mg tablet 0.69 USD tablet
Lozide 2.5 mg Tablet 0.55 USD tablet
Apo-Indapamide 2.5 mg Tablet 0.31 USD tablet
Mylan-Indapamide 2.5 mg Tablet 0.31 USD tablet
Novo-Indapamide 2.5 mg Tablet 0.31 USD tablet
Nu-Indapamide 2.5 mg Tablet 0.31 USD tablet
Pms-Indapamide 2.5 mg Tablet 0.31 USD tablet
Apo-Indapamide 1.25 mg Tablet 0.2 USD tablet
Mylan-Indapamide 1.25 mg Tablet 0.2 USD tablet
Pms-Indapamide 1.25 mg Tablet 0.2 USD tablet
Patents Not Available
Properties
State solid
Melting point 161 oC
Experimental Properties
Property Value Source
water solubility 75 mg/L PhysProp
logP 2.2 PhysProp
pKa 8.8 Various sources
Predicted Properties
Property Value Source
water solubility 3.42e-02 g/l ALOGPS
logP 2.52 ALOGPS
logP 2.43 ChemAxon Molconvert
logS -4.03 ALOGPS
pKa 11.69 ChemAxon Molconvert
hydrogen acceptor count 4 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 92.50 ChemAxon Molconvert
rotatable bond count 3 ChemAxon Molconvert
refractivity 103.31 ChemAxon Molconvert
polarizability 36.34 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Dong DL, Wang QH, Yue P, Jiao JD, Gu RM, Yang BF: Indapamide induces apoptosis of GH3 pituitary cells independently of its inhibition of voltage-dependent K+ currents. Eur J Pharmacol. 2006 Apr 24;536(1-2):78-84. Epub 2006 Mar 2. Pubmed
External Links
Resource Link
KEGG Drug D00345 Link_out
PubChem Compound 3702 Link_out
PubChem Substance 46508626 Link_out
ChemSpider 3574 Link_out
BindingDB 25901 Link_out
Therapeutic Targets Database DAP000498 Link_out
PharmGKB PA449975 Link_out
Drug Product Database 2240350 Link_out
RxList http://www.rxlist.com/cgi/generic/indap.htm Link_out
Drugs.com http://www.drugs.com/cdi/indapamide.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/loz1241.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Indapamide Link_out
ATC Codes
  • C03BA11
AHFS Codes
  • 40:28.24
PDB Entries Not Available
FDA label show (321.9 KB)
MSDS show (72.7 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Take without regard to meals. Magnesium, potassium and zinc needs increased.
Targets

1. Potassium voltage-gated channel subfamily KQT member 1

Pharmacological action: yes
Actions: inhibitor

Probably important in cardiac repolarization. Associates with KCNE1 (MinK) to form the I(Ks) cardiac potassium current. Elicits a rapidly activating, potassium-selective outward current. Muscarinic agonist oxotremorine-M strongly suppresses KCNQ1/KCNE1 current in CHO cells in which cloned KCNQ1/KCNE1 channels were coexpressed with M1 muscarinic receptors. May associate also with KCNE3 (MiRP2) to form the potassium channel that is important for cyclic AMP-stimulated intestinal secretion of chloride ions, which is reduced in cystic fibrosis and pathologically stimulated in cholera and other forms of secretory diarrhea

Organism class: human
UniProt ID: P51787 Link_out
Gene: KCNQ1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Ohya S, Asakura K, Muraki K, Watanabe M, Imaizumi Y: Molecular and functional characterization of ERG, KCNQ, and KCNE subtypes in rat stomach smooth muscle. Am J Physiol Gastrointest Liver Physiol. 2002 Feb;282(2):G277-87. Pubmed
  2. Li RA, Miake J, Hoppe UC, Johns DC, Marban E, Nuss HB: Functional consequences of the arrhythmogenic G306R KvLQT1 K+ channel mutant probed by viral gene transfer in cardiomyocytes. J Physiol. 2001 May 15;533(Pt 1):127-33. Pubmed
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Potassium voltage-gated channel subfamily E member 1

Pharmacological action: yes
Actions: inhibitor

Ancillary protein that assembles as a beta subunit with a voltage-gated potassium channel complex of pore-forming alpha subunits. Modulates the gating kinetics and enhances stability of the channel complex. Assembled with KCNQ1/KVLQT1 is proposed to form the slowly activating delayed rectifier cardiac potassium (IKs) channel. The outward current reaches its steady state only after 50 seconds. Assembled with KCNH2/HERG may modulate the rapidly activating component of the delayed rectifying potassium current in heart (IKr)

Organism class: human
UniProt ID: P15382 Link_out
Gene: KCNE1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Ohya S, Asakura K, Muraki K, Watanabe M, Imaizumi Y: Molecular and functional characterization of ERG, KCNQ, and KCNE subtypes in rat stomach smooth muscle. Am J Physiol Gastrointest Liver Physiol. 2002 Feb;282(2):G277-87. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Sun H, Moore C, Dansette PM, Kumar S, Halpert JR, Yost GS: Dehydrogenation of the indoline-containing drug 4-chloro-N-(2-methyl-1-indolinyl)-3-sulfamoylbenzamide (indapamide) by CYP3A4: correlation with in silico predictions. Drug Metab Dispos. 2009 Mar;37(3):672-84. Epub 2008 Dec 12. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:43

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.