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Record Information
Creation Date2012-09-06 15:16:51 UTC
Update Date2016-02-11 01:32:04 UTC
Secondary Accession NumbersNone
Metabolite Identification
Common NameDiazoxide
DescriptionDiazoxide is only found in individuals that have used or taken this drug. It is a benzothiadiazine derivative that is a peripheral vasodilator used for hypertensive emergencies. It lacks diuretic effect, apparently because it lacks a sulfonamide group. [PubChem]As a diuretic, diazoxide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like diazoxide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of diazoxide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle. As a antihypoglycemic, diazoxide inhibits insulin release from the pancreas, probably by opening potassium channels in the beta cell membrane.
Chemical FormulaC8H7ClN2O2S
Average Molecular Weight230.671
Monoisotopic Molecular Weight229.991675875
IUPAC Name7-chloro-3-methyl-4H-1λ⁶,2,4-benzothiadiazine-1,1-dione
Traditional Namehyperstat
CAS Registry Number364-98-7
InChI Identifier
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as 1,2,4-benzothiadiazine-1,1-dioxides. These are aromatic heterocyclic compounds containing a 1,2,4-benzothiadiazine ring system with two S=O bonds at the 1-position.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganoheterocyclic compounds
Sub ClassThiadiazines
Direct Parent1,2,4-benzothiadiazine-1,1-dioxides
Alternative Parents
  • 1,2,4-benzothiadiazine-1,1-dioxide
  • Aryl chloride
  • Aryl halide
  • Benzenoid
  • Imidolactam
  • Organosulfonic acid or derivatives
  • Organic sulfonic acid or derivatives
  • Azacycle
  • Amidine
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Organic nitrogen compound
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
StatusExpected but not Quantified
  • Drug
  • Antihypertensive Agents
  • Diuretics, Thiazide
  • Vasodilator Agents
  • Pharmaceutical
Cellular locations
  • Cytoplasm
  • Membrane
Physical Properties
Experimental Properties
Melting Point330.5 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility5.52e-01 g/LNot Available
LogP1.3Not Available
Predicted Properties
Water Solubility0.55 mg/mLALOGPS
pKa (Strongest Acidic)10.48ChemAxon
pKa (Strongest Basic)1.33ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area58.53 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity54.84 m3·mol-1ChemAxon
Polarizability20.98 Å3ChemAxon
Number of Rings2ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01119
  • Not Applicable
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01119
  • Not Applicable
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01119
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID2911
KEGG Compound IDC06949
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkDiazoxide
NuGOwiki LinkHMDB15251
Metagene LinkHMDB15251
METLIN IDNot Available
PubChem Compound3019
PDB IDNot Available
ChEBI ID4495
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General ReferencesNot Available


General function:
Involved in glutamate-ammonia ligase activity
Specific function:
This enzyme has 2 functions: it catalyzes the production of glutamine and 4-aminobutanoate (gamma-aminobutyric acid, GABA), the latter in a pyridoxal phosphate-independent manner (By similarity). Essential for proliferation of fetal skin fibroblasts.
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  1. Velloso LA, Bjork E, Ballagi AE, Funa K, Andersson A, Kampe O, Karlsson FA, Eizirik DL: Regulation of GAD expression in islets of Langerhans occurs both at the mRNA and protein level. Mol Cell Endocrinol. 1994 Jun;102(1-2):31-7. [7926271 ]
General function:
Involved in ATP binding
Specific function:
This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients.
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  1. Lawrence CL, Rainbow RD, Davies NW, Standen NB: Effect of metabolic inhibition on glimepiride block of native and cloned cardiac sarcolemmal K(ATP) channels. Br J Pharmacol. 2002 Jul;136(5):746-52. [12086984 ]
  2. Guo W, Chen N, Chen Y, Xia Q, Shen Y: Activation of Mitochondrial ATP-Sensitive Potassium Channel Contributes to Protective Effect in Prolonged Myocardial Preservation. Conf Proc IEEE Eng Med Biol Soc. 2005;4:4027-30. [17281115 ]
  3. Comelli M, Metelli G, Mavelli I: Downmodulation of mitochondrial F0F1 ATP synthase by diazoxide in cardiac myoblasts: a dual effect of the drug. Am J Physiol Heart Circ Physiol. 2007 Feb;292(2):H820-9. [17287451 ]
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)
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  1. Klockner U, Trieschmann U, Isenberg G: Pharmacological modulation of calcium and potassium channels in isolated vascular smooth muscle cells. Arzneimittelforschung. 1989 Jan;39(1A):120-6. [2541731 ]
  2. O'Malley D, Shanley LJ, Harvey J: Insulin inhibits rat hippocampal neurones via activation of ATP-sensitive K+ and large conductance Ca2+-activated K+ channels. Neuropharmacology. 2003 Jun;44(7):855-63. [12726817 ]
  3. Zhang L, Li X, Zhou R, Xing G: Possible role of potassium channel, big K in etiology of schizophrenia. Med Hypotheses. 2006;67(1):41-3. Epub 2006 Jan 30. [16446048 ]
General function:
Involved in carbonate dehydratase activity
Specific function:
Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
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  1. Domoki F, Bari F, Nagy K, Busija DW, Siklos L: Diazoxide prevents mitochondrial swelling and Ca2+ accumulation in CA1 pyramidal cells after cerebral ischemia in newborn pigs. Brain Res. 2004 Sep 3;1019(1-2):97-104. [15306243 ]
  2. Erdemli G, Krnjevic K: Diazoxide suppresses slowly-inactivating outward and inward currents in CA1 hippocampal neurones. Neuroreport. 1993 Dec 13;5(3):249-51. [8298083 ]
  3. Erdemli G, Krnjevic K: Actions of diazoxide on CA1 neurons in hippocampal slices from rats. Can J Physiol Pharmacol. 1995 May;73(5):608-18. [7585327 ]
  4. Scuvee-Moreau J, Seutin V, Vrijens B, Pirotte B, De Tullio P, Massotte L, Albert A, Delarge J, Dresse A: Effect of potassium channel openers on the firing rate of hippocampal pyramidal cells and A10 dopaminergic neurons in vitro. Arch Physiol Biochem. 1997 Sep;105(5):421-8. [9439778 ]
  5. Crepel V, Rovira C, Ben-Ari Y: The K+ channel opener diazoxide enhances glutamatergic currents and reduces GABAergic currents in hippocampal neurons. J Neurophysiol. 1993 Feb;69(2):494-503. [7681475 ]
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.
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  1. Munoz A, Nakazaki M, Goodman JC, Barrios R, Onetti CG, Bryan J, Aguilar-Bryan L: Ischemic preconditioning in the hippocampus of a knockout mouse lacking SUR1-based K(ATP) channels. Stroke. 2003 Jan;34(1):164-70. [12511769 ]
  2. Sekine N, Ullrich S, Regazzi R, Pralong WF, Wollheim CB: Postreceptor signalling of growth hormone and prolactin and their effects in the differentiated insulin-secreting cell line, INS-1. Endocrinology. 1996 May;137(5):1841-50. [8612523 ]
General function:
Involved in inward rectifier potassium channel activity
Specific function:
This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium
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  1. D'hahan N, Moreau C, Prost AL, Jacquet H, Alekseev AE, Terzic A, Vivaudou M: Pharmacological plasticity of cardiac ATP-sensitive potassium channels toward diazoxide revealed by ADP. Proc Natl Acad Sci U S A. 1999 Oct 12;96(21):12162-7. [10518593 ]
  2. Sakura H, Trapp S, Liss B, Ashcroft FM: Altered functional properties of KATP channel conferred by a novel splice variant of SUR1. J Physiol. 1999 Dec 1;521 Pt 2:337-50. [10581306 ]
  3. Shindo T, Katayama Y, Horio Y, Kurachi Y: MCC-134, a novel vascular relaxing agent, is an inverse agonist for the pancreatic-type ATP-sensitive K(+) channel. J Pharmacol Exp Ther. 2000 Jan;292(1):131-5. [10604939 ]
  4. de Lonlay P, Fournet JC, Touati G, Groos MS, Martin D, Sevin C, Delagne V, Mayaud C, Chigot V, Sempoux C, Brusset MC, Laborde K, Bellane-Chantelot C, Vassault A, Rahier J, Junien C, Brunelle F, Nihoul-Fekete C, Saudubray JM, Robert JJ: Heterogeneity of persistent hyperinsulinaemic hypoglycaemia. A series of 175 cases. Eur J Pediatr. 2002 Jan;161(1):37-48. [11808879 ]
  5. Russ U, Lange U, Loffler-Walz C, Hambrock A, Quast U: Binding and effect of K ATP channel openers in the absence of Mg2+. Br J Pharmacol. 2003 May;139(2):368-80. [12770942 ]
General function:
Involved in transport
Specific function:
Electrically silent transporter system. Mediates sodium and chloride reabsorption
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  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]