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Record Information
Version3.6
Creation Date2006-05-18 08:41:17 UTC
Update Date2014-09-23 05:28:12 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
  1. 3,4-Dihydrochlorothiazide
  2. Acuretic
  3. Aldactazide
  4. Aldoril
  5. Apresazide
  6. Aquarills
  7. Aquarius
  8. Bremil
  9. Caplaril
  10. Capozide
  11. Chlorosulthiadil
  12. Chlorothiazide
  13. Chlorsulfonamidodihydrobenzothiadiazine dioxide
  14. Chlorzide
  15. Cidrex
  16. Dichlorosal
  17. Dichlotiazid
  18. Dichlotride
  19. Diclotride
  20. Dihydrochlorothiazid
  21. Dihydrochlorothiazide
  22. Dihydrochlorothiazidum
  23. Dihydrochlorurit
  24. Dihydrochlorurite
  25. Dihydroxychlorothiazidum
  26. Direma
  27. Disalunil
  28. Diuril
  29. Drenol
  30. Dyazide
  31. Esidrex
  32. Esidrix
  33. Esimil
  34. Fluvin
  35. HCTZ
  36. HCZ
  37. Hidril
  38. Hidrochlortiazid
  39. Hidroronol
  40. Hidrotiazida
  41. Hydril
  42. Hydro-Aquil
  43. Hydro-D
  44. Hydro-Diuril
  45. Hydrochloro Thiazide
  46. Hydrochlorothiazid
  47. Hydrochlorothiazide
  48. Hydrochlorothiazide Intensol
  49. Hydrochlorthiazide
  50. Hydrodiuretic
  51. Hydrodiuril
  52. Hydropres
  53. Hydrosaluric
  54. Hydrothide
  55. Hydrozide
  56. Hypothiazid
  57. Hypothiazide
  58. Hyzaar
  59. Idrotiazide
  60. Inderide
  61. Ivaugan
  62. Jen-Diril
  63. Lopressor HCT
  64. Lotensin HCT
  65. Maschitt
  66. Maxzide
  67. Megadiuril
  68. Microzide
  69. Moduretic
  70. Nefrix
  71. Neo-codema
  72. Neoflumen
  73. Newtolide
  74. Oretic
  75. Panurin
  76. Prinzide
  77. Ro-hydrazide
  78. Ser-Ap-Es
  79. Servithiazid
  80. Thiaretic
  81. Thiuretic
  82. Thlaretic
  83. Timolide
  84. Unipres
  85. Urodiazin
  86. Vaseretic
  87. Vetidrex
  88. Ziac
  89. Zide
Chemical FormulaC7H8ClN3O4S2
Average Molecular Weight297.739
Monoisotopic Molecular Weight296.964474846
IUPAC Name6-chloro-1,1-dioxo-3,4-dihydro-2H-1$l^{6},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 KeyJZUFKLXOESDKRF-UHFFFAOYSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAromatic Heteropolycyclic Compounds
ClassBenzothiadiazines
Sub ClassN/A
Other Descriptors
  • Benzenesulfonamides
Substituents
  • Aminal
  • Aryl Chloride
  • Chlorobenzene
  • Organochloride
  • Sulfonamide
  • Sulfonyl
  • Thiadiazine
Direct ParentBenzothiadiazines
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 g/LALOGPS
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 Area118.36ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity63.11ChemAxon
Polarizability25.35ChemAxon
Spectra
SpectraMS/MS1D NMR2D NMR
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biofluid Locations
  • Blood
  • Urine
Tissue Location
  • Adipose Tissue
  • Kidney
  • Platelet
PathwaysNot 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. Pubmed: 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. Pubmed: 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. Pubmed: 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. Pubmed: 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. Pubmed: 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. Pubmed: 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. Pubmed: 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. Pubmed: 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. Pubmed: 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. Pubmed: 3540504
  11. Angelin B: Effect of thiazide treatment on biliary lipid composition in healthy volunteers. Eur J Clin Pharmacol. 1989;37(1):95-6. Pubmed: 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. Pubmed: 9406146
  13. Tisdall PA, Moyer TP, Anhalt JP: Liquid-chromatographic detection of thiazide diuretics in urine. Clin Chem. 1980 May;26(6):702-6. Pubmed: 7371146
  14. Beermann B, Fahraeus L, Groschinsky-Grind M, Lindstrom B: Placental transfer of hydrochlorothiazide. Gynecol Obstet Invest. 1980;11(1):45-8. Pubmed: 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. Pubmed: 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