DIAZOXIDE CHOLINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C8H6ClN2O2S.C5H14NO
Molecular Weight	333.834
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[N+](C)(C)CCO.CC1=NC2=C(C=C(Cl)C=C2)S(=O)(=O)[N-]1

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

Molecular Formula	C5H13NO
Molecular Weight	103.1628
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C8H7ClN2O2S
Molecular Weight	230.671
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 8429	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

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
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
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

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: Cataracts... AEs leading to discontinuation/dose reduction: Cataracts 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 Condition: hypoglycemia hyperinsulinism 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
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
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
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 Condition: hypoglycemia hyperinsulinism 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 2

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
GLUT2 8	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/15845921/	yes
GLUT4 17	inducer 1573 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
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
eMolecules	1934615	https://www.emolecules.com/cgi-bin/more?vid=1934615
eMolecules	36757797	https://www.emolecules.com/cgi-bin/more?vid=36757797

PubMed

Title	Date	PubMed
Development and management of extrapyramidal symptoms in hypertensive patients treated with diazoxide.	1975 Mar	1114967
Intracellular potassium and chloride channels: an update.	2001	11440163
Glucose and insulin stimulate heparin-releasable lipoprotein lipase activity in mouse islets and INS-1 cells. A potential link between insulin resistance and beta-cell dysfunction.	2001 Apr 13	11154699
Laparoscopic pancreatectomy for persistent hyperinsulinemic hypoglycemia of infancy.	2001 Aug	11443431
Effects of bezafibrate on beta-cell function of rat pancreatic islets.	2001 Aug 31	11527545
Hyperinsulinism of infancy: the regulated release of insulin by KATP channel-independent pathways.	2001 Feb	11272144
Effects of glucose and amino acids on free ADP in betaHC9 insulin-secreting cells.	2001 Feb	11272139
Bioenergetic consequences of opening the ATP-sensitive K(+) channel of heart mitochondria.	2001 Feb	11158963
Diazoxide and trimethaphan used?	2001 Jan	11157632
Insulin autoimmune syndrome: the second Dutch case.	2001 Jan	11137746
Role of mitochondrial and sarcolemmal K(ATP) channels in ischemic preconditioning of the canine heart.	2001 Jan	11123240
Direct activation of mitochondrial K(ATP) channels mimics preconditioning but protein kinase C activation is less effective in middle-aged rat hearts.	2001 Jan	11121796
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	11480549
Intrinsic optical signals in respiratory brain stem regions of mice: neurotransmitters, neuromodulators, and metabolic stress.	2001 Jul	11431521
Distinct effect of diazoxide on insulin secretion stimulated by protein kinase A and protein kinase C in rat pancreatic islets.	2001 Jul	11378208
Downregulation of protein kinase C inhibits activation of mitochondrial K(ATP) channels by diazoxide.	2001 Jul 3	11435343
Role of intracellular Na(+) kinetics in preconditioned rat heart.	2001 Jun 8	11397784
Neurologic outcomes of 90 neonates and infants with persistent hyperinsulinemic hypoglycemia.	2001 Mar	11230585
Pituitary adenylate cyclase-activating polypeptide activates K(ATP) current in rat atrial myocytes.	2001 Mar	11179047
Overexpression of a modified human malonyl-CoA decarboxylase blocks the glucose-induced increase in malonyl-CoA level but has no impact on insulin secretion in INS-1-derived (832/13) beta-cells.	2001 Mar 2	11113153
Functional roles of cardiac and vascular ATP-sensitive potassium channels clarified by Kir6.2-knockout mice.	2001 Mar 30	11282890
The role of cyclic AMP in the pathogenesis of glucose desensitization in rat pancreatic islets.	2001 May	11345144
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	11713640
The potential antidiabetic activity of some alpha-2 adrenoceptor antagonists.	2001 Nov	11712871
Mitochondrial ATP-sensitive potassium channels attenuate matrix Ca(2+) overload during simulated ischemia and reperfusion: possible mechanism of cardioprotection.	2001 Nov 9	11701616
Opening of mitochondrial K(ATP) channels attenuates the ouabain-induced calcium overload in mitochondria.	2001 Nov 9	11701611
Contribution to glucose tolerance of insulin-independent vs. insulin-dependent mechanisms in mice.	2001 Oct	11551845
Glucose effects on gastric motility and tone evoked from the rat dorsal vagal complex.	2001 Oct 1	11579164
[Activation of ATP-sensitive K+ channels by ADP and K+ channel openers: homology model of sulfonylurea receptor carboxyl-termini].	2001 Sep	11577458
Synthesis and characterization of a quinolinonic compound activating ATP-sensitive K(+) channels in endocrine and smooth muscle tissues.	2001 Sep	11564656
Diazoxide induced cardioprotection: what comes first, K(ATP) channels or reactive oxygen species?	2001 Sep	11530096
Mitochondrial K(ATP) channel activation reduces anoxic injury by restoring mitochondrial membrane potential.	2001 Sep	11514300
Amino acids and insulin are both required to regulate assembly of the eIF4E. eIF4G complex in rat skeletal muscle.	2001 Sep	11500312

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.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:40:37 UTC 2023` Edited by `admin` on `Fri Dec 15 16:40:37 UTC 2023`
Record UNII	2U8NRZ7P8L
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DIAZOXIDE CHOLINE

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

428214