You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Record Information
Version3.6
Creation Date2006-05-18 08:41:17 UTC
Update Date2016-02-11 01:05:07 UTC
HMDB IDHMDB01928
Secondary Accession NumbersNone
Metabolite Identification
Common NameHydrochlorothiazide
DescriptionHydrochlorothiazide is a thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It has been used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism. -- Pubchem. Hydrochlorothiazide (Apo-Hydro, Aquazide H, Microzide, Oretic), sometimes abbreviated HCT, HCTZ, or HZT is a popular diuretic drug that acts by inhibiting the kidney's ability to retain water. This reduces the volume of the blood, decreasing peripheral vascular resistance. Chlorothiazide, a carbonic anhydrase inhibitor. --Wikipedia.
Structure
Thumb
Synonyms
ValueSource
EsidrixChEBI
HidroclorotiazidaChEBI
HydrochlorothiazidumChEBI
3,4-DihydrochlorothiazideHMDB
AcureticHMDB
AldactazideHMDB
AldorilHMDB
ApresazideHMDB
AquarillsHMDB
AquariusHMDB
BremilHMDB
CaplarilHMDB
CapozideHMDB
ChlorosulthiadilHMDB
ChlorothiazideHMDB
Chlorsulfonamidodihydrobenzothiadiazine dioxideHMDB
ChlorzideHMDB
CidrexHMDB
DichlorosalHMDB
DichlotiazidHMDB
DichlotrideHMDB
DiclotrideHMDB
DihydrochlorothiazidHMDB
DihydrochlorothiazideHMDB
DihydrochlorothiazidumHMDB
DihydrochloruritHMDB
DihydrochloruriteHMDB
DihydroxychlorothiazidumHMDB
DiremaHMDB
DisalunilHMDB
DiurilHMDB
DrenolHMDB
DyazideHMDB
EsidrexHMDB
EsimilHMDB
FluvinHMDB
HCTZHMDB
HCZHMDB
HidrilHMDB
HidrochlortiazidHMDB
HidroronolHMDB
HidrotiazidaHMDB
HydrilHMDB
hydro-AquilHMDB
hydro-DHMDB
hydro-DiurilHMDB
hydrochloro ThiazideHMDB
HydrochlorothiazidHMDB
Hydrochlorothiazide intensolHMDB
HydrochlorthiazideHMDB
HydrodiureticHMDB
HydrodiurilHMDB
HydropresHMDB
HydrosaluricHMDB
HydrothideHMDB
HydrozideHMDB
HypothiazidHMDB
HypothiazideHMDB
HyzaarHMDB
IdrotiazideHMDB
InderideHMDB
IvauganHMDB
Jen-dirilHMDB
Lopressor HCTHMDB
Lotensin HCTHMDB
MaschittHMDB
MaxzideHMDB
MegadiurilHMDB
MicrozideHMDB
ModureticHMDB
NefrixHMDB
neo-CodemaHMDB
NeoflumenHMDB
NewtolideHMDB
OreticHMDB
PanurinHMDB
PrinzideHMDB
ro-HydrazideHMDB
Ser-ap-esHMDB
ServithiazidHMDB
ThiareticHMDB
ThiureticHMDB
ThlareticHMDB
TimolideHMDB
UnipresHMDB
UrodiazinHMDB
VasereticHMDB
VetidrexHMDB
ZiacHMDB
ZideHMDB
Chemical FormulaC7H8ClN3O4S2
Average Molecular Weight297.739
Monoisotopic Molecular Weight296.964474846
IUPAC Name6-chloro-1,1-dioxo-3,4-dihydro-2H-1λ⁶,2,4-benzothiadiazine-7-sulfonamide
Traditional Namehydrochlorothiazide
CAS Registry Number58-93-5
SMILES
NS(=O)(=O)C1=C(Cl)C=C2NCNS(=O)(=O)C2=C1
InChI Identifier
InChI=1S/C7H8ClN3O4S2/c8-4-1-5-7(2-6(4)16(9,12)13)17(14,15)11-3-10-5/h1-2,10-11H,3H2,(H2,9,12,13)
InChI KeyInChIKey=JZUFKLXOESDKRF-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as benzothiadiazines. These are organic compounds containing a benzene fused to a thiadiazine ring (a six-member ring with two nitrogen atoms and a sulfur atom).
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassThiadiazines
Sub ClassBenzothiadiazines
Direct ParentBenzothiadiazines
Alternative Parents
Substituents
  • Benzothiadiazine
  • Benzenesulfonamide
  • Secondary aliphatic/aromatic amine
  • Chlorobenzene
  • Benzenoid
  • Aryl halide
  • Aryl chloride
  • Aminosulfonyl compound
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • Azacycle
  • Secondary amine
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Ontology
StatusDetected and Quantified
Origin
  • Drug
BiofunctionNot Available
ApplicationNot Available
Cellular locations
  • Cytoplasm (predicted from logP)
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point274 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.722 mg/mL at 25 °CNot Available
LogP-0.07HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility2.24 mg/mLALOGPS
logP-0.16ALOGPS
logP-0.58ChemAxon
logS-2.1ALOGPS
pKa (Strongest Acidic)9.09ChemAxon
pKa (Strongest Basic)-2.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area118.36 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity63.11 m3·mol-1ChemAxon
Polarizability25.35 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-052b-0090000000-aaa48e4702874457ae26View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0r6r-0920000000-b129acf72e7dde12441eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0a4i-1900000000-67f803f38aed0bd12adeView in MoNA
MSMass Spectrum (Electron Ionization)splash10-00r2-6490000000-3f5d9320308b823c6489View in MoNA
1D NMR1H NMR SpectrumNot Available
1D NMR1H NMR SpectrumNot Available
1D NMR13C NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biofluid Locations
  • Blood
  • Urine
Tissue Location
  • Adipose Tissue
  • Kidney
  • Platelet
Pathways
NameSMPDB LinkKEGG Link
Hydrochlorothiazide PathwaySMP00100Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.3 (0.00167-0.67) uMAdult (>18 years old)BothNormal details
UrineDetected but not QuantifiedNot ApplicableNot AvailableNot AvailableNormal details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiofluidValueOriginal ageOriginal sexOriginal conditionComments
Blood0-2 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00999
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022745
KNApSAcK IDNot Available
Chemspider ID3513
KEGG Compound IDC07041
BioCyc ID12-DEHYDRORETICULINIUM
BiGG IDNot Available
Wikipedia LinkHydrochlorothiazide
NuGOwiki LinkHMDB01928
Metagene LinkHMDB01928
METLIN ID3169
PubChem Compound3639
PDB IDHCZ
ChEBI ID102045
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Splendiani G, Condo S: [Diuretic therapy in heart failure] G Ital Nefrol. 2006 Jan-Feb;23 Suppl 34:S74-6. [16634001 ]
  2. Dimitriadis G, Tegos C, Golfinopoulou L, Roboti C, Raptis S: Furosemide-induced hyperglycaemia: the implication of glycolytic kinases. Horm Metab Res. 1993 Nov;25(11):557-9. [8288156 ]
  3. Vandenheuvel WJ, Gruber VF, Walker RW, Wolf FJ: GLC analysis of hydrochlorothiazide in blood and plasma. J Pharm Sci. 1975 Aug;64(8):1309-12. [1151702 ]
  4. Yamazaki M, Ito Y, Suzuka T, Yaginuma H, Itoh S, Kamada A, Orita Y, Nakahama H, Nakanishi T, Ando A: Biopharmaceutical studies of thiazide diuretics. II. High-performance liquid chromatographic method for determination of hydrochlorothiazide in plasma, urine, blood cells and bile. Chem Pharm Bull (Tokyo). 1984 Jun;32(6):2387-94. [6488407 ]
  5. Germano G, Sanguigni V, Pignatelli P, Caccese D, Lenti L, Ragazzo M, Lauro R, Violi F: Enhanced platelet release of superoxide anion in systemic hypertension: role of AT1 receptors. J Hypertens. 2004 Jun;22(6):1151-6. [15167450 ]
  6. Bernik MM, Heimann JC, Nakandakare ER, Cazita PM, Nunes VS, Rocha JC, Neves MQ, Quintao EC: Effects of hydrochlorothiazide and propranolol treatment on chylomicron metabolism in hypertensive objects. Can J Physiol Pharmacol. 2005 Jul;83(7):617-23. [16091787 ]
  7. Dornhorst A, Powell SH, Pensky J: Aggravation by propranolol of hyperglycaemic effect of hydrochlorothiazide in type II diabetics without alteration of insulin secretion. Lancet. 1985 Jan 19;1(8421):123-6. [2857210 ]
  8. Serradeil-Le Gal C, Lacour C, Valette G, Garcia G, Foulon L, Galindo G, Bankir L, Pouzet B, Guillon G, Barberis C, Chicot D, Jard S, Vilain P, Garcia C, Marty E, Raufaste D, Brossard G, Nisato D, Maffrand JP, Le Fur G: Characterization of SR 121463A, a highly potent and selective, orally active vasopressin V2 receptor antagonist. J Clin Invest. 1996 Dec 15;98(12):2729-38. [8981918 ]
  9. Kuo BS, Mandagere A, Osborne DR, Hwang KK: Column-switching high-performance liquid chromatographic (HPLC) determination of hydrochlorothiazide in rat, dog, and human plasma. Pharm Res. 1990 Dec;7(12):1257-61. [2095563 ]
  10. Cubeddu LX, Hoffmann IS, Davila S, Escontrelas C, Morales C, Rios A: Effects of propranolol, clonidine and hydrochlorothiazide treatment and abrupt discontinuation on central and peripheral noradrenergic activity in essential hypertension. Life Sci. 1986 Dec 22;39(25):2463-74. [3540504 ]
  11. Angelin B: Effect of thiazide treatment on biliary lipid composition in healthy volunteers. Eur J Clin Pharmacol. 1989;37(1):95-6. [2591472 ]
  12. Buttar HS: An overview of the influence of ACE inhibitors on fetal-placental circulation and perinatal development. Mol Cell Biochem. 1997 Nov;176(1-2):61-71. [9406146 ]
  13. Tisdall PA, Moyer TP, Anhalt JP: Liquid-chromatographic detection of thiazide diuretics in urine. Clin Chem. 1980 May;26(6):702-6. [7371146 ]
  14. Beermann B, Fahraeus L, Groschinsky-Grind M, Lindstrom B: Placental transfer of hydrochlorothiazide. Gynecol Obstet Invest. 1980;11(1):45-8. [7390276 ]
  15. Vonaparti A, Kazanis M, Panderi I: Development and validation of a liquid chromatographic/electrospray ionization mass spectrometric method for the determination of benazepril, benazeprilat and hydrochlorothiazide in human plasma. J Mass Spectrom. 2006 May;41(5):593-605. [16541390 ]

Enzymes

General function:
Involved in ion channel activity
Specific function:
Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+). It is also activated by the concentration of cytosolic Mg(2+). Its activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays a key role in controlling excitability in a number of systems, such as regulation of the contraction of smooth muscle, the tuning of hair cells in the cochlea, regulation of transmitter release, and innate immunity. In smooth muscles, its activation by high level of Ca(2+), caused by ryanodine receptors in the sarcoplasmic reticulum, regulates the membrane potential. In cochlea cells, its number and kinetic properties partly determine the characteristic frequency of each hair cell and thereby helps to establish a tonotopic map. Kinetics of KCNMA1 channels are determined by alternative splicing, phosphorylation status and its combination with modulating beta subunits. Highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX)
Gene Name:
KCNMA1
Uniprot ID:
Q12791
Molecular weight:
137558.1
General function:
Involved in carbonate dehydratase activity
Specific function:
Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
Gene Name:
CA1
Uniprot ID:
P00915
Molecular weight:
28870.0
General function:
Involved in carbonate dehydratase activity
Specific function:
Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye.
Gene Name:
CA2
Uniprot ID:
P00918
Molecular weight:
29245.895
General function:
Involved in transport
Specific function:
Electrically silent transporter system. Mediates sodium and chloride reabsorption
Gene Name:
SLC12A3
Uniprot ID:
P55017
Molecular weight:
113124.0
General function:
Involved in carbonate dehydratase activity
Specific function:
Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid.
Gene Name:
CA4
Uniprot ID:
P22748
Molecular weight:
35032.075