DIAZOXIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C8H7ClN2O2S
Molecular Weight	230.671
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=NC2=CC=C(Cl)C=C2S(=O)(=O)N1

InChI

InChIKey=GDLBFKVLRPITMI-UHFFFAOYSA-N

InChI=1S/C8H7ClN2O2S/c1-5-10-7-3-2-6(9)4-8(7)14(12,13)11-5/h2-4H,1H3,(H,10,11)

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf

Diazoxide is a drug which was approved by FDA for the treatment of secondary hyperinsulinemia. The drug exerts its action by binding to SUR1 subunit of ATP-sensitive potassium channel that leads to the channel opening.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Sulfonylurea receptor 1, Kir6.2 13 Target ID: CHEMBL2096972 Sources: https://www.researchgate.net/publication/234093464_Diazoxide	Opener 34		10.94 µM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hyperinsulinemia 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf	Primary		Approved 8583	PROGLYCEM Approved Use Proglycem (ORAL DIAZOXIDE) is useful in the management of hypoglycemia due to hyperinsulinism associated with the following conditions: Inoperable islet cell adenoma or carcinoma, or extrapancreatic malignancy in adults. Infants and Children: Leucine sensitivity, islet cell hyperplasia, nesidioblastosis, extrapancreatic malignancy, islet cell adenoma, or adenomatosis. Launch Date 1976

C_max

Value	Dose	Co-administered	Analyte	Population
45 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28715810/	2.5 mg 3 times / day steady-state, oral dose: 2.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		DIAZOXIDE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
345 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28715810/	2.5 mg 3 times / day steady-state, oral dose: 2.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		DIAZOXIDE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
14.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28715810/	2.5 mg 3 times / day steady-state, oral dose: 2.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		DIAZOXIDE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: MALE food status: UNKNOWN
30 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf	2.5 mg/kg 3 times / day multiple, oral dose: 2.5 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered:		DIAZOXIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
10% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf	2.5 mg/kg 3 times / day multiple, oral dose: 2.5 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered:		DIAZOXIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
8 mg/kg 1 times / day multiple, oral Dose: 8 mg/kg, 1 times / day Route: oral Route: multiple Dose: 8 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf	unhealthy, adult + children Health Status: unhealthy Age Group: adult + children Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf	Disc. AE: Hyperosmolar (non-ketotic) coma... AEs leading to discontinuation/dose reduction: Hyperosmolar (non-ketotic) coma Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf
8 mg/kg 1 times / day multiple, oral Dose: 8 mg/kg, 1 times / day Route: oral Route: multiple Dose: 8 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf	Disc. AE: Diabetic hyperosmolar coma... AEs leading to discontinuation/dose reduction: Diabetic hyperosmolar coma Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf
8 mg/kg 1 times / day multiple, oral Dose: 8 mg/kg, 1 times / day Route: oral Route: multiple Dose: 8 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf	unhealthy, children Health Status: unhealthy Age Group: children Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf	Disc. AE: Musculoskeletal and connective tissue deformities of skull, face and buccal cavity... AEs leading to discontinuation/dose reduction: Musculoskeletal and connective tissue deformities of skull, face and buccal cavity (4 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf
8 mg/kg 1 times / day multiple, oral Dose: 8 mg/kg, 1 times / day Route: oral Route: multiple Dose: 8 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf	unhealthy, children Health Status: unhealthy Age Group: children Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf	Disc. AE: Cataracts... AEs leading to discontinuation/dose reduction: Cataracts Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf
15 mg/kg 1 times / day multiple, oral Dose: 15 mg/kg, 1 times / day Route: oral Route: multiple Dose: 15 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf	unhealthy, infant + neonates Health Status: unhealthy Age Group: infant + neonates Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf	Disc. AE: Pulmonary hypertension... AEs leading to discontinuation/dose reduction: Pulmonary hypertension Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf

AEs

AE	Significance	Dose	Population
Hyperosmolar (non-ketotic) coma	Disc. AE	8 mg/kg 1 times / day multiple, oral Dose: 8 mg/kg, 1 times / day Route: oral Route: multiple Dose: 8 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf	unhealthy, adult + children Health Status: unhealthy Age Group: adult + children Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf
Diabetic hyperosmolar coma	Disc. AE	8 mg/kg 1 times / day multiple, oral Dose: 8 mg/kg, 1 times / day Route: oral Route: multiple Dose: 8 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf
Musculoskeletal and connective tissue deformities of skull, face and buccal cavity	4 patients Disc. AE	8 mg/kg 1 times / day multiple, oral Dose: 8 mg/kg, 1 times / day Route: oral Route: multiple Dose: 8 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf	unhealthy, children Health Status: unhealthy Age Group: children Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf
Cataracts	Disc. AE	8 mg/kg 1 times / day multiple, oral Dose: 8 mg/kg, 1 times / day Route: oral Route: multiple Dose: 8 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf	unhealthy, children Health Status: unhealthy Age Group: children Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf
Pulmonary hypertension	Disc. AE	15 mg/kg 1 times / day multiple, oral Dose: 15 mg/kg, 1 times / day Route: oral Route: multiple Dose: 15 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf	unhealthy, infant + neonates Health Status: unhealthy Age Group: infant + neonates Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017453s020lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
		GLUT2 4 GLUT4 5

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
GLUT2 8	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/15845921/	yes
GLUT4 20	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/14976464/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4495	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4495
ChemicalBook	CB8426893	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8426893
eMolecules	1934615	https://www.emolecules.com/cgi-bin/more?vid=1934615
eMolecules	36757797	https://www.emolecules.com/cgi-bin/more?vid=36757797
MolPort	MolPort-003-666-772	https://www.molport.com/shop/molecule-link/MolPort-003-666-772
MolPort	MolPort-003-941-186	https://www.molport.com/shop/molecule-link/MolPort-003-941-186
ZINC	ZINC000003872277	http://zinc15.docking.org/substances/ZINC000003872277

PubMed

Title	Date	PubMed
Mitochondrial ATP-sensitive potassium channels attenuate matrix Ca(2+) overload during simulated ischemia and reperfusion: possible mechanism of cardioprotection.	2001-11-09	11701616
Opening of mitochondrial K(ATP) channels attenuates the ouabain-induced calcium overload in mitochondria.	2001-11-09	11701611
Mitochondrial ATP-sensitive channel opener does not induce vascular preconditioning, but potentiates the effect of a preconditioning ischemia on coronary reactive hyperemia in the anesthetized goat.	2001-11	11713640
The potential antidiabetic activity of some alpha-2 adrenoceptor antagonists.	2001-11	11712871
Mitochondrial K(ATP) channel as an end effector of cardioprotection during late preconditioning: triggering role of nitric oxide.	2001-11	11708847
Management of hyperinsulinemia with diazoxide in an elderly hemodialysis patient.	2001-11	11598399
Ischemic and pharmacological preconditioning in Girardi cells and C2C12 myotubes induce mitochondrial uncoupling.	2001-10-26	11679408
Glucose effects on gastric motility and tone evoked from the rat dorsal vagal complex.	2001-10-01	11579164
The KATP channel opener diazoxide protects cardiac myocytes during metabolic inhibition without causing mitochondrial depolarization or flavoprotein oxidation.	2001-10	11588107
Effect of aging on the ability of preconditioning to protect rat hearts from ischemia-reperfusion injury.	2001-10	11557553
Contribution to glucose tolerance of insulin-independent vs. insulin-dependent mechanisms in mice.	2001-10	11551845
Identification and pharmacological correction of a membrane trafficking defect associated with a mutation in the sulfonylurea receptor causing familial hyperinsulinism.	2001-09-21	11457841
Identification and properties of a novel intracellular (mitochondrial) ATP-sensitive potassium channel in brain.	2001-09-07	11441006
Incorporation of sulfonylurea into N-isopropylacrylamide as an extracellular matrix for an artificial pancreas.	2001-09	11676014
Critical timing of mitochondrial K(ATP) channel opening for enhancement of myocardial tolerance against infarction.	2001-09	11605991
[Activation of ATP-sensitive K+ channels by ADP and K+ channel openers: homology model of sulfonylurea receptor carboxyl-termini].	2001-09	11577458
Lidocaine and mexiletine inhibit mitochondrial oxidation in rat ventricular myocytes.	2001-09	11575552
Synthesis and characterization of a quinolinonic compound activating ATP-sensitive K(+) channels in endocrine and smooth muscle tissues.	2001-09	11564656
Mitochondrial K(ATP) channel opening protects a human atrial-derived cell line by a mechanism involving free radical generation.	2001-09	11530102
Diazoxide induced cardioprotection: what comes first, K(ATP) channels or reactive oxygen species?	2001-09	11530096
Contribution of both the sarcolemmal K(ATP) and mitochondrial K(ATP) channels to infarct size limitation by K(ATP) channel openers: differences from preconditioning in the role of sarcolemmal K(ATP) channels.	2001-09	11521165
Hyperinsulinism and hyperammonemia syndrome: report of twelve unrelated patients.	2001-09	11518822
Hepatothermic therapy of obesity: rationale and an inventory of resources.	2001-09	11516225
Mitochondrial K(ATP) channel activation reduces anoxic injury by restoring mitochondrial membrane potential.	2001-09	11514300
Amino acids and insulin are both required to regulate assembly of the eIF4E. eIF4G complex in rat skeletal muscle.	2001-09	11500312
Effects of bezafibrate on beta-cell function of rat pancreatic islets.	2001-08-31	11527545
Modulation of islet ATP content by inhibition or stimulation of the Na(+)/K(+) pump.	2001-08-24	11525782
Inhibition of large-conductance calcium-activated potassium channel by 2-methoxyestradiol in cultured vascular endothelial (HUV-EC-C) cells.	2001-08-01	11547343
Sulfonylurea receptors inhibit the epithelial sodium channel (ENaC) by reducing surface expression.	2001-08	11512032
Acute insulin responses to leucine in children with the hyperinsulinism/hyperammonemia syndrome.	2001-08	11502802
Hyperinsulinism in short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency reveals the importance of beta-oxidation in insulin secretion.	2001-08	11489939
ATP-sensitive K+ channels and cellular actions of morphine in periaqueductal gray slices of neonatal and adult rats.	2001-08	11454910
Laparoscopic pancreatectomy for persistent hyperinsulinemic hypoglycemia of infancy.	2001-08	11443431
Downregulation of protein kinase C inhibits activation of mitochondrial K(ATP) channels by diazoxide.	2001-07-03	11435343
Effect on insulin release of compounds structurally related to the potassium-channel opener 7-chloro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide (BPDZ 73): introduction of heteroatoms on the 3-alkylamino side chain of the benzothiadiazine 1,1-dioxide ring.	2001-07	11480549
Intrinsic optical signals in respiratory brain stem regions of mice: neurotransmitters, neuromodulators, and metabolic stress.	2001-07	11431521
Oral agents for the treatment of type 2 diabetes mellitus: pharmacology, toxicity, and treatment.	2001-07	11423816
Glimepiride, a novel sulfonylurea, does not abolish myocardial protection afforded by either ischemic preconditioning or diazoxide.	2001-06-26	11425777
Mitochondrial ATP-sensitive potassium channels inhibit apoptosis induced by oxidative stress in cardiac cells.	2001-06-22	11420303
Role of intracellular Na(+) kinetics in preconditioned rat heart.	2001-06-08	11397784
Store-operated influx of Ca(2+) in pancreatic beta-cells exhibits graded dependence on the filling of the endoplasmic reticulum.	2001-06	11493653
Transient hyperinsulinism in an asphyxiated newborn infant with hypoglycemia.	2001-06	11444360
Restoration of Ca2+-inhibited oxidative phosphorylation in cardiac mitochondria by mitochondrial Ca2+ unloading.	2001-04	11451373
Interaction of sulfonylurea-conjugated polymer with insulinoma cell line of MIN6 and its effect on insulin secretion.	2001-04	11426400
Mitochondrial ATP-sensitive K+ channels play a role in cardioprotection by Na+-H+ exchange inhibition against ischemia/reperfusion injury.	2001-03-01	11693777
Failure to precondition pathological human myocardium.	2001-03-01	11693741
Disopyramide and its metabolite enhance insulin release from clonal pancreatic beta-cells by blocking K(ATP) channels.	2001-01	11504161
Modulation of beta-cell ouabain-sensitive 86Rb+ influx (Na+/K+ pump) by D-glucose, glibenclamide or diazoxide.	2001	11467417
Intracellular potassium and chloride channels: an update.	2001	11440163
Mitochondrial ATP-sensitive potassium channel plays a dominant role in ischemic preconditioning of rabbit heart.	2001	11399869

Patents

Sample Use Guides

In Vivo Use Guide

Adults and children: The usual daily dosage is 3 to 8 mg/kg, divided into two or three equal doses every 8 or 12 hours. Infants and newborns: The usual daily dosage is 8 to 15 mg/kg divided into two or three equal doses every 8 to 12 hours. An appropriate starting dosage is 10 mg/kg/day, divided into three equal doses every 8 hours.

Route of Administration: Oral

In Vitro Use Guide

Diazoxide inhibited glucagon secretion in rat pancreas at concentration of 325 uM.

Name

Type

Language

HYPERSTAT

Preferred Name

English

DIAZOXIDE

Official Name

English

EUDEMINE INJECTION

Common Name

English

DIAZOXIDE [EP MONOGRAPH]

Common Name

English

7-Chloro-3-methyl-2H-1,2,4-benzothiadiazine 1,1-dioxide

Systematic Name

English

DIAZOXIDE [MI]

Common Name

English

SCH-6783

Code

English

DIAZOXIDE [ORANGE BOOK]

Common Name

English

SCH 6783

Code

English

Diazoxide [WHO-DD]

Common Name

English

DIAZOXIDE [VANDF]

Common Name

English

DIAZOXIDE [USP-RS]

Common Name

English

DIAZOXIDE [USP MONOGRAPH]

Common Name

English

2H-1,2,4-BENZOTHIADIAZINE, 7-CHLORO-3-METHYL-, 1,1-DIOXIDE

Systematic Name

English

HYPERTONALUM

Common Name

English

DIAZOXIDE [MART.]

Common Name

English

DIAZOXIDE [JAN]

Common Name

English

PROGLYCEM

Brand Name

English

diazoxide [INN]

Common Name

English

DIAZOXIDUM [WHO-IP LATIN]

Common Name

English

SRG-95213

Code

English

SRG 95213

Code

English

NSC-76130

Code

English

DIAZOXIDE [WHO-IP]

Common Name

English

DIAZOXIDE [USAN]

Common Name

English

NSC-64198

Code

English

Classification Tree Code System Code

WHO-ATC

V03AH01