INDAPAMIDE HEMIHYDRATE

Details

Stereochemistry	RACEMIC
Molecular Formula	2C16H16ClN3O3S.H2O
Molecular Weight	749.684
Optical Activity	( + / - )
Defined Stereocenters	0 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.CC1CC2=C(C=CC=C2)N1NC(=O)C3=CC=C(Cl)C(=C3)S(N)(=O)=O.CC4CC5=C(C=CC=C5)N4NC(=O)C6=CC=C(Cl)C(=C6)S(N)(=O)=O

InChI

InChIKey=GPFKQEHXQLDCEK-UHFFFAOYSA-N

InChI=1S/2C16H16ClN3O3S.H2O/c2*1-10-8-11-4-2-3-5-14(11)20(10)19-16(21)12-6-7-13(17)15(9-12)24(18,22)23;/h2*2-7,9-10H,8H2,1H3,(H,19,21)(H2,18,22,23);1H2

HIDE SMILES / InChI

Molecular Formula	H2O
Molecular Weight	18.0153
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C16H16ClN3O3S
Molecular Weight	365.835
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: http://www.drugbank.ca/drugs/DB00808
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/dosage/indapamide.html

Indapamide is an antihypertensive and a diuretic. It contains both a polar sulfamoyl chlorobenzamide moiety and a lipid- soluble methylindoline moiety. 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. Indapamide is used 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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Voltage-gated potassium channel subunit Kv7.1 3 Target ID: CHEMBL1866 Sources: http://www.drugbank.ca/drugs/DB00808	Inhibitor 8297
Voltage-gated potassium channel beta subunit Mink 3 Target ID: CHEMBL4872 Sources: http://www.drugbank.ca/drugs/DB00808	Inhibitor 8297
Carbonic anhydrase IX 35 Target ID: CHEMBL3594 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19119014	Inhibitor 8297	36.0 nM [Ki]
Carbonic anhydrase XII 30 Target ID: CHEMBL3242 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19119014	Inhibitor 8297	10.0 nM [Ki]
Carbonic anhydrase VII 34 Target ID: CHEMBL2326 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19119014	Inhibitor 8297	0.23 nM [Ki]
Thiazide-sensitive sodium-chloride cotransporter 28 Target ID: CHEMBL1876 Sources: http://www.genome.jp/dbget-bin/www_bget?dr:D00345	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Congestive heart failure 54 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/98/75-105_Indapamide_prntlbl.pdf	Primary		Approved 8429	Indapamide Approved Use Indapamide tablets are indicated for the treatment of hypertension, alone or in combination with other antihypertensive drugs. Indapamide tablets are also indicated for the treatment of salt and fluid retention associated with congestive heart failure. Launch Date 1998
Hypertension 567 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/98/75-105_Indapamide_prntlbl.pdf	Primary		Approved 8429	Indapamide Approved Use Indapamide tablets are indicated for the treatment of hypertension, alone or in combination with other antihypertensive drugs. Indapamide tablets are also indicated for the treatment of salt and fluid retention associated with congestive heart failure. Launch Date 1998

C_max

Value	Dose	Co-administered	Analyte	Population
260 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/018538s028lbl.pdf	5 g single, oral dose: 5 g route of administration: Oral experiment type: SINGLE co-administered:		INDAPAMIDE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
47.79 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23447043	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:		INDAPAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
919.52 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23447043	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:		INDAPAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
14 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/018538s028lbl.pdf	5 g single, oral dose: 5 g route of administration: Oral experiment type: SINGLE co-administered:		INDAPAMIDE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
23.23 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23447043	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:		INDAPAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
25% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/018538s028lbl.pdf	5 g single, oral dose: 5 g route of administration: Oral experiment type: SINGLE co-administered:		INDAPAMIDE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
2.5 mg 1 times / day multiple, oral Recommended Dose: 2.5 mg, 1 times / day Route: oral Route: multiple Dose: 2.5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6346848 Page: p.261	unhealthy, 21 - 73 n = 311 Health Status: unhealthy Condition: Hypertension Age Group: 21 - 73 Sex: M+F Population Size: 311 Sources: https://pubmed.ncbi.nlm.nih.gov/6346848 Page: p.261	Disc. AE: Hypokalemia... AEs leading to discontinuation/dose reduction: Hypokalemia (0.64%) Sources: https://pubmed.ncbi.nlm.nih.gov/6346848 Page: p.261

AEs

AE	Significance	Dose	Population
Hypokalemia	0.64% Disc. AE	2.5 mg 1 times / day multiple, oral Recommended Dose: 2.5 mg, 1 times / day Route: oral Route: multiple Dose: 2.5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6346848 Page: p.261	unhealthy, 21 - 73 n = 311 Health Status: unhealthy Condition: Hypertension Age Group: 21 - 73 Sex: M+F Population Size: 311 Sources: https://pubmed.ncbi.nlm.nih.gov/6346848 Page: p.261

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	substrate 1037		inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT3 642 OATP1B3 706	CYP2C19 991 CYP2C8 693	CYP2C23 10 CYP4A1 17

Drug as perpetrator

Target	Modality	Activity
CYP4A1 25	inducer 1573 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3716319/	no
OAT3 644	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17314201/	yes [IC50 11 uM]
OATP1B3 715	inhibitor 3277 Sources: https://molpharm.aspetjournals.org/content/83/6/1257	yes [Inhibition 10 uM]
CYP2C23 10	inducer 1573 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3716319/	yes

Drug as victim

Target	Modality	Activity
CYP3A4 1737	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2645476/	major
CYP2C19 991	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2645476/	yes
CYP2C8 693	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2645476/	yes
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22579001/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/7923634/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:5893	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:5893
ChemicalBook	CB2420420	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2420420
MolPort	MolPort-003-666-209	https://www.molport.com/shop/molecule-link/MolPort-003-666-209
Selleck Chemicals	Indapamide(Lozol)	http://www.selleckchem.com/products/Indapamide(Lozol).html
eMolecules	539574	https://www.emolecules.com/cgi-bin/more?vid=539574

PubMed

Title	Date	PubMed
Antihypertensive action of indapamide. Comparative studies in several experimental models.	1975 Oct	1243026
Progress in reducing the burden of stroke.	2001 Dec	11903323
The lowering of blood pressure after stroke.	2001 Dec 8	11747944
The lowering of blood pressure after stroke.	2001 Dec 8	11747943
Stripping voltammetric determination of indapamide in serum at castor oil-based carbon paste electrodes.	2001 Jan	11199220
Effects of combination of low doses of angiotensin-converting enzyme inhibitor and diuretics on renal function in spontaneously hypertensive rats: comparison between acute and chronic treatment.	2001 Jun	11881108
Pharmacoutilization of antihypertensive drugs: a model of analysis.	2001 Jun	11430633
Coversyl plus--when monotherapy is not enough.	2001 Jun-Jul	11710312
New benefits of blood pressure lowering treatments for millions of stroke sufferers.	2001 Jun-Jul	11710310
Improvement in blood pressure, arterial stiffness and wave reflections with a very-low-dose perindopril/indapamide combination in hypertensive patient: a comparison with atenolol.	2001 Oct	11641310
[CEA comprehensive evaluation for Western and traditional Chinese hypotensive drugs].	2001 Sep	12575552
Blood pressure and stroke; the PROGRESS trial.	2001 Sep	11881116
Growth inhibitory activity of indapamide on vascular smooth muscle cells.	2001 Sep 28	11779033
[Clinical assessment of efficacy and safety of noliprel in patients with hypertension].	2002	12494074
Cutaneous drug reaction case reports: from the world literature.	2002	11978142
[Efficacy and tolerance of rilmenidine in patients with mild to moderate hypertension. Results of a Czech and Slovak 6-month multicenter study].	2002 Aug	12425202
Gender influence on the dose-ranging of a low-dose perindopril-indapamide combination in hypertension: effect on systolic and pulse pressure.	2002 Aug	12172328
[Indapamide-induced pemphigus foliaceus a sulfurous affair?].	2002 Aug-Sep	12442120
Effects of four antihypertensive monotherapies on cardiac mass and function in hypertensive patients with left ventricular hypertrophy: randomized prospective study.	2002 Dec	12476475
Hypokalaemia and hyponatraemia due to indapamide.	2002 Dec	12472097
Very-low-dose combination of the angiotensin-converting enzyme inhibitor perindopril and the diuretic indapamide induces an early and sustained increase in neovascularization in rat ischemic legs.	2002 Dec	12438525
Efficacious response with low-dose indapamide therapy in the treatment of type II diabetic patients with normal renal function or moderate renal insufficiency and moderate hypertension.	2002 Jan-Feb	11919395
Comparison of indapamide and low-dose hydrochlorothiazide monotherapy in black patients with mild to moderate hypertension.	2002 Jul	12197195
Hyponatraemia and hypokalaemia due to indapamide.	2002 Mar 4	11999238
Fixed combinations of delapril plus indapamide vs fosinopril plus hydrochlorothiazide in mild to moderate essential hypertension.	2002 May-Jun	12201354
Efficacy of very low dose perindopril 2 mg/indapamide 0.625 mg combination on left ventricular hypertrophy in hypertensive patients: the P.I.C.X.E.L. study rationale and design.	2002 Sep	12214263
Dose-dependent prevention of fibrosis in aorta of salt-loaded stroke-prone spontaneously hypertensive rats by combined delapril and indapamide treatment.	2002 Sep	12198325
Two derivative spectrophotometric determinations of indapamide in pharmaceutical dosage forms.	2002 Sep 5	12191722
Drug-drug interactions among elderly patients hospitalized for drug toxicity.	2003 Apr 2	12672733
[Secondary prevention after ischemic stroke].	2003 Jan 29	12643070
Cardiovascular protective role of a low-dose antihypertensive combination in obese Zucker rats.	2003 Mar	12640256
Effects of a perindopril-based blood pressure lowering regimen on cardiac outcomes among patients with cerebrovascular disease.	2003 Mar	12633548
Effect of low-dose perindopril/indapamide on albuminuria in diabetes: preterax in albuminuria regression: PREMIER.	2003 May	12654706
Optimization of a solid-phase extraction method for determination of indapamide in biological fluids using high-performance liquid chromatography.	2003 May 5	12668086

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Edema Initial dose: 2.5 mg orally once a day. Usual Adult Dose for Hypertension Initial dose: 1.25 mg orally once a day.

Route of Administration: Oral

In Vitro Use Guide

10(-4) M Indapamide decreased bone resorption in organ cultures and in cocultures of osteoblast-like cells and bone marrow cells in the presence of 10(-8) M 1,25-dihydroxyvitamin D3

Substance Class	Chemical Created by `admin` on `Sat Dec 16 09:06:24 GMT 2023` Edited by `admin` on `Sat Dec 16 09:06:24 GMT 2023`
Record UNII	W0LY35K007
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

INDAPAMIDE HEMIHYDRATE

Common Name

English

BENZAMIDE, 3-(AMINOSULFONYL)-4-CHLORO-N-(2,3-DIHYDRO-2-METHYL-1H-INDOL-1-YL)-, HYDRATE (2:1)

Systematic Name

English

4-CHLORO-N-(2-METHYL-2,3-DIHYDRO-1H-INDOL-1-YL)-3-SULFAMOYLBENZAMIDE HYDRATE (2:1)

Systematic Name

English

D06401

Code

English

Indapamide hemihydrate [WHO-DD]

Common Name

English

TENAXIL

Brand Name

English

INDAPAMIDE HYDRATE

Common Name

English

Code System Code Type Description

FDA UNII

W0LY35K007