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Details

Stereochemistry ACHIRAL
Molecular Formula C8H6ClN2O2S.C5H14NO
Molecular Weight 333.8357
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DIAZOXIDE CHOLINE

SMILES

CC1=Nc2ccc(cc2S(=O)(=O)[N-]1)Cl.C[N+](C)(C)CCO

InChI

InChIKey=YLLWQNAEYILHLV-UHFFFAOYSA-N
InChI=1S/C8H6ClN2O2S.C5H14NO/c1-5-10-7-3-2-6(9)4-8(7)14(12,13)11-5;1-6(2,3)4-5-7/h2-4H,1H3;7H,4-5H2,1-3H3/q-1;+1

HIDE SMILES / InChI
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

Sources: www.ncbi.nlm.nih.gov/pubmed/22056385

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
10.94 µM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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

2.02089595E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
45 μg/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
345 μg × h/mL
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
30 h
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
14.3 h
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
10%
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

Doses

DosePopulationAdverse 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:
unhealthy, adult + children
Health Status: unhealthy
Age Group: adult + children
Sources:
Disc. AE: Hyperosmolar (non-ketotic) coma...
AEs leading to
discontinuation/dose reduction:
Hyperosmolar (non-ketotic) coma
Sources:
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:
unhealthy, adult
Disc. AE: Diabetic hyperosmolar coma...
AEs leading to
discontinuation/dose reduction:
Diabetic hyperosmolar coma
Sources:
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:
unhealthy, children
Health Status: unhealthy
Age Group: children
Sources:
Disc. AE: Cataracts...
AEs leading to
discontinuation/dose reduction:
Cataracts
Sources:
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:
unhealthy, children
Health Status: unhealthy
Condition: hypoglycemia hyperinsulinism
Age Group: children
Sources:
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:
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:
unhealthy, infant + neonates
Health Status: unhealthy
Age Group: infant + neonates
Sources:
Disc. AE: Pulmonary hypertension...
AEs leading to
discontinuation/dose reduction:
Pulmonary hypertension
Sources:
AEs

AEs

AESignificanceDosePopulation
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:
unhealthy, adult + children
Health Status: unhealthy
Age Group: adult + children
Sources:
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:
unhealthy, adult
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:
unhealthy, children
Health Status: unhealthy
Age Group: children
Sources:
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:
unhealthy, children
Health Status: unhealthy
Condition: hypoglycemia hyperinsulinism
Age Group: children
Sources:
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:
unhealthy, infant + neonates
Health Status: unhealthy
Age Group: infant + neonates
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes
yes
PubMed

PubMed

TitleDatePubMed
Modulation of beta-cell ouabain-sensitive 86Rb+ influx (Na+/K+ pump) by D-glucose, glibenclamide or diazoxide.
2001
Intracellular potassium and chloride channels: an update.
2001
Mitochondrial ATP-sensitive potassium channel plays a dominant role in ischemic preconditioning of rabbit heart.
2001
Restoration of Ca2+-inhibited oxidative phosphorylation in cardiac mitochondria by mitochondrial Ca2+ unloading.
2001 Apr
Interaction of sulfonylurea-conjugated polymer with insulinoma cell line of MIN6 and its effect on insulin secretion.
2001 Apr
Sulfonylurea receptors inhibit the epithelial sodium channel (ENaC) by reducing surface expression.
2001 Aug
Acute insulin responses to leucine in children with the hyperinsulinism/hyperammonemia syndrome.
2001 Aug
Hyperinsulinism in short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency reveals the importance of beta-oxidation in insulin secretion.
2001 Aug
ATP-sensitive K+ channels and cellular actions of morphine in periaqueductal gray slices of neonatal and adult rats.
2001 Aug
Laparoscopic pancreatectomy for persistent hyperinsulinemic hypoglycemia of infancy.
2001 Aug
Inhibition of large-conductance calcium-activated potassium channel by 2-methoxyestradiol in cultured vascular endothelial (HUV-EC-C) cells.
2001 Aug 1
Modulation of islet ATP content by inhibition or stimulation of the Na(+)/K(+) pump.
2001 Aug 24
Effects of bezafibrate on beta-cell function of rat pancreatic islets.
2001 Aug 31
Disopyramide and its metabolite enhance insulin release from clonal pancreatic beta-cells by blocking K(ATP) channels.
2001 Jan
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 Jul
Intrinsic optical signals in respiratory brain stem regions of mice: neurotransmitters, neuromodulators, and metabolic stress.
2001 Jul
Oral agents for the treatment of type 2 diabetes mellitus: pharmacology, toxicity, and treatment.
2001 Jul
Downregulation of protein kinase C inhibits activation of mitochondrial K(ATP) channels by diazoxide.
2001 Jul 3
Store-operated influx of Ca(2+) in pancreatic beta-cells exhibits graded dependence on the filling of the endoplasmic reticulum.
2001 Jun
Transient hyperinsulinism in an asphyxiated newborn infant with hypoglycemia.
2001 Jun
Mitochondrial ATP-sensitive potassium channels inhibit apoptosis induced by oxidative stress in cardiac cells.
2001 Jun 22
Glimepiride, a novel sulfonylurea, does not abolish myocardial protection afforded by either ischemic preconditioning or diazoxide.
2001 Jun 26
Role of intracellular Na(+) kinetics in preconditioned rat heart.
2001 Jun 8
Mitochondrial ATP-sensitive K+ channels play a role in cardioprotection by Na+-H+ exchange inhibition against ischemia/reperfusion injury.
2001 Mar 1
Failure to precondition pathological human myocardium.
2001 Mar 1
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 Nov
The potential antidiabetic activity of some alpha-2 adrenoceptor antagonists.
2001 Nov
Mitochondrial K(ATP) channel as an end effector of cardioprotection during late preconditioning: triggering role of nitric oxide.
2001 Nov
Management of hyperinsulinemia with diazoxide in an elderly hemodialysis patient.
2001 Nov
Mitochondrial ATP-sensitive potassium channels attenuate matrix Ca(2+) overload during simulated ischemia and reperfusion: possible mechanism of cardioprotection.
2001 Nov 9
Opening of mitochondrial K(ATP) channels attenuates the ouabain-induced calcium overload in mitochondria.
2001 Nov 9
The KATP channel opener diazoxide protects cardiac myocytes during metabolic inhibition without causing mitochondrial depolarization or flavoprotein oxidation.
2001 Oct
Effect of aging on the ability of preconditioning to protect rat hearts from ischemia-reperfusion injury.
2001 Oct
Contribution to glucose tolerance of insulin-independent vs. insulin-dependent mechanisms in mice.
2001 Oct
Glucose effects on gastric motility and tone evoked from the rat dorsal vagal complex.
2001 Oct 1
Ischemic and pharmacological preconditioning in Girardi cells and C2C12 myotubes induce mitochondrial uncoupling.
2001 Oct 26
Incorporation of sulfonylurea into N-isopropylacrylamide as an extracellular matrix for an artificial pancreas.
2001 Sep
Critical timing of mitochondrial K(ATP) channel opening for enhancement of myocardial tolerance against infarction.
2001 Sep
[Activation of ATP-sensitive K+ channels by ADP and K+ channel openers: homology model of sulfonylurea receptor carboxyl-termini].
2001 Sep
Lidocaine and mexiletine inhibit mitochondrial oxidation in rat ventricular myocytes.
2001 Sep
Synthesis and characterization of a quinolinonic compound activating ATP-sensitive K(+) channels in endocrine and smooth muscle tissues.
2001 Sep
Mitochondrial K(ATP) channel opening protects a human atrial-derived cell line by a mechanism involving free radical generation.
2001 Sep
Diazoxide induced cardioprotection: what comes first, K(ATP) channels or reactive oxygen species?
2001 Sep
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 Sep
Hyperinsulinism and hyperammonemia syndrome: report of twelve unrelated patients.
2001 Sep
Hepatothermic therapy of obesity: rationale and an inventory of resources.
2001 Sep
Mitochondrial K(ATP) channel activation reduces anoxic injury by restoring mitochondrial membrane potential.
2001 Sep
Amino acids and insulin are both required to regulate assembly of the eIF4E. eIF4G complex in rat skeletal muscle.
2001 Sep
Identification and pharmacological correction of a membrane trafficking defect associated with a mutation in the sulfonylurea receptor causing familial hyperinsulinism.
2001 Sep 21
Identification and properties of a novel intracellular (mitochondrial) ATP-sensitive potassium channel in brain.
2001 Sep 7
Patents

Sample Use Guides

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
DIAZOXIDE CHOLINE
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 428214
Created by admin on Fri Jun 25 23:25:37 UTC 2021 , Edited by admin on Fri Jun 25 23:25:37 UTC 2021
EU-Orphan Drug EU/3/17/1941
Created by admin on Fri Jun 25 23:25:37 UTC 2021 , Edited by admin on Fri Jun 25 23:25:37 UTC 2021
Code System Code Type Description
FDA UNII
2U8NRZ7P8L
Created by admin on Fri Jun 25 23:25:37 UTC 2021 , Edited by admin on Fri Jun 25 23:25:37 UTC 2021
PRIMARY
CAS
1098065-76-9
Created by admin on Fri Jun 25 23:25:37 UTC 2021 , Edited by admin on Fri Jun 25 23:25:37 UTC 2021
PRIMARY
PUBCHEM
25014811
Created by admin on Fri Jun 25 23:25:37 UTC 2021 , Edited by admin on Fri Jun 25 23:25:37 UTC 2021
PRIMARY