Identification

Name
Diazoxide
Accession Number
DB01119  (APRD00914)
Type
Small Molecule
Groups
Approved
Description

A benzothiadiazine derivative that is a peripheral vasodilator used for hypertensive emergencies. It lacks diuretic effect, apparently because it lacks a sulfonamide group. [PubChem]

Structure
Thumb
Synonyms
  • Diazossido
  • Diazoxide
  • Diazoxido
  • Diazoxidum
  • Eudemine
External IDs
NSC-64198 / NSC-76130 / SCH 6783 / SCH-6783 / SRG 95213 / SRG-95213
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Hyperstat Inj 15mg/mlLiquid15 mgIntravenousSchering Plough1973-12-312003-07-14Canada
ProglycemCapsule100 mgOralMerck Ltd.1985-12-31Not applicableCanada
ProglycemSuspension50 mg/mLOralTeva Branded Pharmaceutical Products, R&D Inc.1990-09-30Not applicableUs
Proglycem Susp 50mg/mlSuspension50 mgOralSchering Plough1984-12-312006-03-23Canada
International/Other Brands
Eudemine (Mercury) / Hyperstat (Schering)
Categories
UNII
O5CB12L4FN
CAS number
364-98-7
Weight
Average: 230.671
Monoisotopic: 229.991675875
Chemical Formula
C8H7ClN2O2S
InChI Key
GDLBFKVLRPITMI-UHFFFAOYSA-N
InChI
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)
IUPAC Name
7-chloro-3-methyl-4H-1λ⁶,2,4-benzothiadiazine-1,1-dione
SMILES
CC1=NS(=O)(=O)C2=C(N1)C=CC(Cl)=C2

Pharmacology

Indication

Used parentally to treat hypertensive emergencies. Also used to treat hypoglycemia secondary to insulinoma.

Structured Indications
Pharmacodynamics

Diazoxide is a potassium channel activator, which causes local relaxation in smooth muscle by increasing membrane permeability to potassium ions. This switches off voltage-gated calcium ion channels which inhibits the generation of an action potential.

Mechanism of action

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.

TargetActionsOrganism
AATP-sensitive inward rectifier potassium channel 11
inducer
Human
ACarbonic anhydrase 1
inhibitor
Human
ACarbonic anhydrase 2
inhibitor
Human
USodium/potassium-transporting ATPase subunit alpha-1
other
Human
UCalcium-activated potassium channel subunit alpha-1
other
Human
USolute carrier family 12 member 3
unknown
Human
Absorption

Readily absorbed following oral administration.

Volume of distribution
Not Available
Protein binding

Very high (more than 90%) to serum proteins.

Metabolism

Hepatic.

Route of elimination

Proglycem is extensively bound (more than 90%) to serum proteins, and is excreted in the kidneys.

Half life

28 ±8.3 hours in normal adults.

Clearance
Not Available
Toxicity

Oral LD50 in rat and mouse: 980 mg/kg and 444 mg/kg, respectively.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Diazoxide.Investigational
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypotensive activities of Diazoxide.Experimental
AcarboseThe therapeutic efficacy of Acarbose can be decreased when used in combination with Diazoxide.Approved, Investigational
AcebutololDiazoxide may increase the hypotensive activities of Acebutolol.Approved
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Diazoxide.Investigational, Withdrawn
AICA ribonucleotideThe therapeutic efficacy of AICA ribonucleotide can be decreased when used in combination with Diazoxide.Experimental, Investigational
AlfuzosinAlfuzosin may increase the hypotensive activities of Diazoxide.Approved, Investigational
AliskirenDiazoxide may increase the hypotensive activities of Aliskiren.Approved, Investigational
AllicinThe therapeutic efficacy of Allicin can be decreased when used in combination with Diazoxide.Investigational
AlogliptinThe therapeutic efficacy of Alogliptin can be decreased when used in combination with Diazoxide.Approved
AlprenololDiazoxide may increase the hypotensive activities of Alprenolol.Approved, Withdrawn
AmbrisentanDiazoxide may increase the hypotensive activities of Ambrisentan.Approved, Investigational
AmifostineDiazoxide may increase the hypotensive activities of Amifostine.Approved, Investigational
AmlodipineDiazoxide may increase the hypotensive activities of Amlodipine.Approved
AmphetamineAmphetamine may increase the hypotensive activities of Diazoxide.Approved, Illicit
AtenololDiazoxide may increase the hypotensive activities of Atenolol.Approved
AvanafilAvanafil may increase the antihypertensive activities of Diazoxide.Approved
BalaglitazoneThe therapeutic efficacy of Balaglitazone can be decreased when used in combination with Diazoxide.Investigational
Bempedoic acidThe therapeutic efficacy of Bempedoic acid can be decreased when used in combination with Diazoxide.Investigational
BenazeprilDiazoxide may increase the hypotensive activities of Benazepril.Approved, Investigational
BendroflumethiazideThe risk or severity of adverse effects can be increased when Bendroflumethiazide is combined with Diazoxide.Approved
BenmoxinBenmoxin may increase the hypotensive activities of Diazoxide.Withdrawn
BepridilDiazoxide may increase the hypotensive activities of Bepridil.Approved, Withdrawn
BetaxololDiazoxide may increase the hypotensive activities of Betaxolol.Approved
BethanidineDiazoxide may increase the hypotensive activities of Bethanidine.Approved
BietaserpineDiazoxide may increase the hypotensive activities of Bietaserpine.Experimental
BimatoprostDiazoxide may increase the hypotensive activities of Bimatoprost.Approved, Investigational
BisoprololDiazoxide may increase the hypotensive activities of Bisoprolol.Approved
BosentanDiazoxide may increase the hypotensive activities of Bosentan.Approved, Investigational
BQ-123Diazoxide may increase the hypotensive activities of BQ-123.Investigational
BretyliumDiazoxide may increase the hypotensive activities of Bretylium.Approved
BrimonidineDiazoxide may increase the hypotensive activities of Brimonidine.Approved
BrofaromineBrofaromine may increase the hypotensive activities of Diazoxide.Experimental
BuforminThe therapeutic efficacy of Buformin can be decreased when used in combination with Diazoxide.Investigational, Withdrawn
BupranololDiazoxide may increase the hypotensive activities of Bupranolol.Approved
CadralazineDiazoxide may increase the hypotensive activities of Cadralazine.Experimental
CafedrineDiazoxide may increase the hypotensive activities of Cafedrine.Investigational
CanagliflozinThe therapeutic efficacy of Canagliflozin can be decreased when used in combination with Diazoxide.Approved
CandesartanDiazoxide may increase the hypotensive activities of Candesartan.Experimental
Candesartan cilexetilDiazoxide may increase the hypotensive activities of Candesartan cilexetil.Approved
CandoxatrilDiazoxide may increase the hypotensive activities of Candoxatril.Experimental
CaptoprilDiazoxide may increase the hypotensive activities of Captopril.Approved
CarbutamideThe therapeutic efficacy of Carbutamide can be decreased when used in combination with Diazoxide.Experimental
CaroxazoneCaroxazone may increase the hypotensive activities of Diazoxide.Withdrawn
CarteololDiazoxide may increase the hypotensive activities of Carteolol.Approved
CarvedilolDiazoxide may increase the hypotensive activities of Carvedilol.Approved, Investigational
CastanospermineThe therapeutic efficacy of Castanospermine can be decreased when used in combination with Diazoxide.Experimental
CeliprololDiazoxide may increase the hypotensive activities of Celiprolol.Approved, Investigational
ChlorothiazideThe risk or severity of adverse effects can be increased when Chlorothiazide is combined with Diazoxide.Approved, Vet Approved
ChlorpropamideThe therapeutic efficacy of Chlorpropamide can be decreased when used in combination with Diazoxide.Approved
ChlorthalidoneThe risk or severity of adverse effects can be increased when Chlorthalidone is combined with Diazoxide.Approved
CicletanineDiazoxide may increase the hypotensive activities of Cicletanine.Investigational
CiglitazoneThe therapeutic efficacy of Ciglitazone can be decreased when used in combination with Diazoxide.Experimental
CilazaprilDiazoxide may increase the hypotensive activities of Cilazapril.Approved
ClonidineDiazoxide may increase the hypotensive activities of Clonidine.Approved
CloranololDiazoxide may increase the hypotensive activities of Cloranolol.Experimental
CryptenamineDiazoxide may increase the hypotensive activities of Cryptenamine.Approved
CyclopenthiazideThe risk or severity of adverse effects can be increased when Cyclopenthiazide is combined with Diazoxide.Experimental
CyclothiazideDiazoxide may increase the hypotensive activities of Cyclothiazide.Approved
DebrisoquinDiazoxide may increase the hypotensive activities of Debrisoquin.Approved, Investigational
DelaprilDiazoxide may increase the hypotensive activities of Delapril.Experimental
DeoxyspergualinThe therapeutic efficacy of Deoxyspergualin can be decreased when used in combination with Diazoxide.Investigational
DeserpidineDiazoxide may increase the hypotensive activities of Deserpidine.Approved
DexketoprofenThe risk or severity of adverse effects can be increased when Dexketoprofen is combined with Diazoxide.Approved, Investigational
diethylnorspermineDiazoxide may increase the hypotensive activities of diethylnorspermine.Investigational
DihydralazineDiazoxide may increase the hypotensive activities of Dihydralazine.Investigational
DiltiazemDiazoxide may increase the hypotensive activities of Diltiazem.Approved
DorzolamideDiazoxide may increase the hypotensive activities of Dorzolamide.Approved
DoxazosinDiazoxide may increase the hypotensive activities of Doxazosin.Approved
DulaglutideThe therapeutic efficacy of Dulaglutide can be decreased when used in combination with Diazoxide.Approved
EfonidipineDiazoxide may increase the hypotensive activities of Efonidipine.Approved
EmpagliflozinThe therapeutic efficacy of Empagliflozin can be decreased when used in combination with Diazoxide.Approved
EnalaprilDiazoxide may increase the hypotensive activities of Enalapril.Approved, Vet Approved
EnalaprilatDiazoxide may increase the hypotensive activities of Enalaprilat.Approved
EndralazineDiazoxide may increase the hypotensive activities of Endralazine.Experimental
EpanololDiazoxide may increase the hypotensive activities of Epanolol.Experimental
EpoprostenolDiazoxide may increase the hypotensive activities of Epoprostenol.Approved
EprosartanDiazoxide may increase the hypotensive activities of Eprosartan.Approved
ExenatideThe therapeutic efficacy of Exenatide can be decreased when used in combination with Diazoxide.Approved, Investigational
FelodipineDiazoxide may increase the hypotensive activities of Felodipine.Approved, Investigational
FenoldopamDiazoxide may increase the hypotensive activities of Fenoldopam.Approved
Ferulic acidDiazoxide may increase the hypotensive activities of Ferulic acid.Experimental
FosinoprilDiazoxide may increase the hypotensive activities of Fosinopril.Approved
FosphenytoinThe serum concentration of Fosphenytoin can be decreased when it is combined with Diazoxide.Approved
FurazolidoneFurazolidone may increase the hypotensive activities of Diazoxide.Approved, Investigational, Vet Approved
GlibornurideThe therapeutic efficacy of Glibornuride can be decreased when used in combination with Diazoxide.Investigational, Withdrawn
GliclazideThe therapeutic efficacy of Gliclazide can be decreased when used in combination with Diazoxide.Approved
GlimepirideThe therapeutic efficacy of Glimepiride can be decreased when used in combination with Diazoxide.Approved
GlipizideThe therapeutic efficacy of Glipizide can be decreased when used in combination with Diazoxide.Approved
GliquidoneThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Diazoxide.Approved, Investigational
GlyburideThe therapeutic efficacy of Glyburide can be decreased when used in combination with Diazoxide.Approved
GuanabenzDiazoxide may increase the hypotensive activities of Guanabenz.Approved, Investigational
GuanadrelDiazoxide may increase the hypotensive activities of Guanadrel.Approved
GuanazodineDiazoxide may increase the hypotensive activities of Guanazodine.Experimental
GuanethidineDiazoxide may increase the hypotensive activities of Guanethidine.Approved
GuanfacineDiazoxide may increase the hypotensive activities of Guanfacine.Approved, Investigational
GuanoclorDiazoxide may increase the hypotensive activities of Guanoclor.Experimental
GuanoxabenzDiazoxide may increase the hypotensive activities of Guanoxabenz.Experimental
GuanoxanDiazoxide may increase the hypotensive activities of Guanoxan.Experimental
GusperimusThe therapeutic efficacy of Gusperimus can be decreased when used in combination with Diazoxide.Investigational
HarmalineHarmaline may increase the hypotensive activities of Diazoxide.Experimental
HexamethoniumDiazoxide may increase the hypotensive activities of Hexamethonium.Experimental
HydracarbazineHydracarbazine may increase the hypotensive activities of Diazoxide.Experimental
HydralazineDiazoxide may increase the hypotensive activities of Hydralazine.Approved
HydrochlorothiazideThe risk or severity of adverse effects can be increased when Hydrochlorothiazide is combined with Diazoxide.Approved, Vet Approved
HydroflumethiazideThe risk or severity of adverse effects can be increased when Hydroflumethiazide is combined with Diazoxide.Approved, Investigational
IloprostIloprost may increase the hypotensive activities of Diazoxide.Approved, Investigational
ImidaprilDiazoxide may increase the hypotensive activities of Imidapril.Investigational
IndapamideThe risk or severity of adverse effects can be increased when Indapamide is combined with Diazoxide.Approved
IndenololDiazoxide may increase the hypotensive activities of Indenolol.Withdrawn
IndoraminDiazoxide may increase the hypotensive activities of Indoramin.Withdrawn
Insulin AspartThe therapeutic efficacy of Insulin Aspart can be decreased when used in combination with Diazoxide.Approved
Insulin DetemirThe therapeutic efficacy of Insulin Detemir can be decreased when used in combination with Diazoxide.Approved
Insulin GlargineThe therapeutic efficacy of Insulin Glargine can be decreased when used in combination with Diazoxide.Approved
Insulin GlulisineThe therapeutic efficacy of Insulin Glulisine can be decreased when used in combination with Diazoxide.Approved
Insulin HumanThe therapeutic efficacy of Insulin Human can be decreased when used in combination with Diazoxide.Approved, Investigational
Insulin LisproThe therapeutic efficacy of Insulin Lispro can be decreased when used in combination with Diazoxide.Approved
Insulin PorkThe therapeutic efficacy of Insulin Pork can be decreased when used in combination with Diazoxide.Approved
IproclozideIproclozide may increase the hypotensive activities of Diazoxide.Withdrawn
IproniazidIproniazid may increase the hypotensive activities of Diazoxide.Withdrawn
IrbesartanDiazoxide may increase the hypotensive activities of Irbesartan.Approved, Investigational
IsocarboxazidIsocarboxazid may increase the hypotensive activities of Diazoxide.Approved
IsradipineDiazoxide may increase the hypotensive activities of Isradipine.Approved
KetanserinDiazoxide may increase the hypotensive activities of Ketanserin.Investigational
LabetalolDiazoxide may increase the hypotensive activities of Labetalol.Approved
LacidipineDiazoxide may increase the hypotensive activities of Lacidipine.Approved, Investigational
LatanoprostDiazoxide may increase the hypotensive activities of Latanoprost.Approved, Investigational
LercanidipineDiazoxide may increase the hypotensive activities of Lercanidipine.Approved, Investigational
LinagliptinThe therapeutic efficacy of Linagliptin can be decreased when used in combination with Diazoxide.Approved
LinsidomineDiazoxide may increase the hypotensive activities of Linsidomine.Experimental
LiraglutideThe therapeutic efficacy of Liraglutide can be decreased when used in combination with Diazoxide.Approved
LisinoprilDiazoxide may increase the hypotensive activities of Lisinopril.Approved, Investigational
LofexidineDiazoxide may increase the hypotensive activities of Lofexidine.Approved, Investigational
LosartanDiazoxide may increase the hypotensive activities of Losartan.Approved
MacitentanDiazoxide may increase the hypotensive activities of Macitentan.Approved
ManidipineDiazoxide may increase the hypotensive activities of Manidipine.Approved, Investigational
MebanazineMebanazine may increase the hypotensive activities of Diazoxide.Withdrawn
MecamylamineDiazoxide may increase the hypotensive activities of Mecamylamine.Approved
MetforminThe therapeutic efficacy of Metformin can be decreased when used in combination with Diazoxide.Approved
MethoserpidineDiazoxide may increase the hypotensive activities of Methoserpidine.Experimental
MethyclothiazideThe risk or severity of adverse effects can be increased when Methyclothiazide is combined with Diazoxide.Approved
MethyldopaDiazoxide may increase the hypotensive activities of Methyldopa.Approved
Methylene blueMethylene blue may increase the hypotensive activities of Diazoxide.Approved, Investigational
MethylphenidateMethylphenidate may decrease the antihypertensive activities of Diazoxide.Approved, Investigational
MetipranololDiazoxide may increase the hypotensive activities of Metipranolol.Approved
MetolazoneThe risk or severity of adverse effects can be increased when Metolazone is combined with Diazoxide.Approved
MetoprololDiazoxide may increase the hypotensive activities of Metoprolol.Approved, Investigational
MetyrosineDiazoxide may increase the hypotensive activities of Metyrosine.Approved
MibefradilDiazoxide may increase the hypotensive activities of Mibefradil.Investigational, Withdrawn
MiglitolThe therapeutic efficacy of Miglitol can be decreased when used in combination with Diazoxide.Approved
MiglustatThe therapeutic efficacy of Miglustat can be decreased when used in combination with Diazoxide.Approved
MinaprineMinaprine may increase the hypotensive activities of Diazoxide.Approved
MinoxidilDiazoxide may increase the hypotensive activities of Minoxidil.Approved
MirodenafilMirodenafil may increase the antihypertensive activities of Diazoxide.Investigational
MitiglinideThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Diazoxide.Approved, Investigational
MoclobemideMoclobemide may increase the hypotensive activities of Diazoxide.Approved
MoexiprilDiazoxide may increase the hypotensive activities of Moexipril.Approved
MolsidomineMolsidomine may increase the hypotensive activities of Diazoxide.Approved, Investigational
MoxonidineDiazoxide may increase the hypotensive activities of Moxonidine.Approved, Investigational
MuzolimineDiazoxide may increase the hypotensive activities of Muzolimine.Experimental
NadololDiazoxide may increase the hypotensive activities of Nadolol.Approved
NaftopidilDiazoxide may increase the hypotensive activities of Naftopidil.Investigational
NateglinideThe therapeutic efficacy of Nateglinide can be decreased when used in combination with Diazoxide.Approved, Investigational
NebivololDiazoxide may increase the hypotensive activities of Nebivolol.Approved, Investigational
NialamideNialamide may increase the hypotensive activities of Diazoxide.Withdrawn
NicardipineDiazoxide may increase the hypotensive activities of Nicardipine.Approved
NicorandilDiazoxide may increase the hypotensive activities of Nicorandil.Approved, Investigational
NiguldipineDiazoxide may increase the hypotensive activities of Niguldipine.Experimental
NilvadipineDiazoxide may increase the hypotensive activities of Nilvadipine.Approved, Investigational
NimodipineDiazoxide may increase the hypotensive activities of Nimodipine.Approved
NisoldipineDiazoxide may increase the hypotensive activities of Nisoldipine.Approved
NitrendipineDiazoxide may increase the hypotensive activities of Nitrendipine.Approved, Investigational
NitroprussideDiazoxide may increase the hypotensive activities of Nitroprusside.Approved
ObinutuzumabDiazoxide may increase the hypotensive activities of Obinutuzumab.Approved
OctamoxinOctamoxin may increase the hypotensive activities of Diazoxide.Withdrawn
OlmesartanDiazoxide may increase the hypotensive activities of Olmesartan.Approved, Investigational
OmapatrilatDiazoxide may increase the hypotensive activities of Omapatrilat.Investigational
OxprenololDiazoxide may increase the hypotensive activities of Oxprenolol.Approved
PargylineDiazoxide may increase the hypotensive activities of Pargyline.Approved
PenbutololDiazoxide may increase the hypotensive activities of Penbutolol.Approved, Investigational
PentoliniumDiazoxide may increase the hypotensive activities of Pentolinium.Approved
PentoxifyllinePentoxifylline may increase the hypotensive activities of Diazoxide.Approved, Investigational
PerindoprilDiazoxide may increase the hypotensive activities of Perindopril.Approved
PhenelzinePhenelzine may increase the hypotensive activities of Diazoxide.Approved
PhenforminThe therapeutic efficacy of Phenformin can be decreased when used in combination with Diazoxide.Approved, Investigational, Withdrawn
PheniprazinePheniprazine may increase the hypotensive activities of Diazoxide.Withdrawn
PhenoxybenzamineDiazoxide may increase the hypotensive activities of Phenoxybenzamine.Approved
PhenoxypropazinePhenoxypropazine may increase the hypotensive activities of Diazoxide.Withdrawn
PhentolamineDiazoxide may increase the hypotensive activities of Phentolamine.Approved
PhenytoinThe serum concentration of Phenytoin can be decreased when it is combined with Diazoxide.Approved, Vet Approved
PinacidilDiazoxide may increase the hypotensive activities of Pinacidil.Withdrawn
PindololDiazoxide may increase the hypotensive activities of Pindolol.Approved
PioglitazoneThe therapeutic efficacy of Pioglitazone can be decreased when used in combination with Diazoxide.Approved, Investigational
PirlindolePirlindole may increase the hypotensive activities of Diazoxide.Approved
PivhydrazinePivhydrazine may increase the hypotensive activities of Diazoxide.Withdrawn
Platelet Activating FactorDiazoxide may increase the hypotensive activities of Platelet Activating Factor.Experimental
PolythiazideThe risk or severity of adverse effects can be increased when Polythiazide is combined with Diazoxide.Approved
PramlintideThe therapeutic efficacy of Pramlintide can be decreased when used in combination with Diazoxide.Approved, Investigational
PrazosinDiazoxide may increase the hypotensive activities of Prazosin.Approved
ProcarbazineProcarbazine may increase the hypotensive activities of Diazoxide.Approved
PropranololDiazoxide may increase the hypotensive activities of Propranolol.Approved, Investigational
QuinaprilDiazoxide may increase the hypotensive activities of Quinapril.Approved, Investigational
QuinethazoneThe risk or severity of adverse effects can be increased when Quinethazone is combined with Diazoxide.Approved
QuinineQuinine may increase the hypotensive activities of Diazoxide.Approved
RamiprilDiazoxide may increase the hypotensive activities of Ramipril.Approved
RasagilineRasagiline may increase the hypotensive activities of Diazoxide.Approved
RemikirenDiazoxide may increase the hypotensive activities of Remikiren.Approved
RepaglinideThe therapeutic efficacy of Repaglinide can be decreased when used in combination with Diazoxide.Approved, Investigational
RescinnamineDiazoxide may increase the hypotensive activities of Rescinnamine.Approved
ReserpineDiazoxide may increase the hypotensive activities of Reserpine.Approved, Investigational
RilmenidineDiazoxide may increase the hypotensive activities of Rilmenidine.Investigational
RiociguatDiazoxide may increase the hypotensive activities of Riociguat.Approved
RituximabDiazoxide may increase the hypotensive activities of Rituximab.Approved
RosiglitazoneThe therapeutic efficacy of Rosiglitazone can be decreased when used in combination with Diazoxide.Approved, Investigational
SafrazineSafrazine may increase the hypotensive activities of Diazoxide.Withdrawn
SaprisartanDiazoxide may increase the hypotensive activities of Saprisartan.Experimental
SaxagliptinThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Diazoxide.Approved
SelegilineSelegiline may increase the hypotensive activities of Diazoxide.Approved, Investigational, Vet Approved
SelexipagDiazoxide may increase the hypotensive activities of Selexipag.Approved
SildenafilSildenafil may increase the antihypertensive activities of Diazoxide.Approved, Investigational
SitagliptinThe therapeutic efficacy of Sitagliptin can be decreased when used in combination with Diazoxide.Approved, Investigational
SitaxentanDiazoxide may increase the hypotensive activities of Sitaxentan.Approved, Investigational, Withdrawn
SotagliflozinThe therapeutic efficacy of Sotagliflozin can be decreased when used in combination with Diazoxide.Investigational
SpiraprilDiazoxide may increase the hypotensive activities of Spirapril.Approved
SulodexideThe therapeutic efficacy of Sulodexide can be decreased when used in combination with Diazoxide.Approved, Investigational
TadalafilTadalafil may increase the antihypertensive activities of Diazoxide.Approved, Investigational
TalinololDiazoxide may increase the hypotensive activities of Talinolol.Investigational
TelmisartanDiazoxide may increase the hypotensive activities of Telmisartan.Approved, Investigational
TemocaprilDiazoxide may increase the hypotensive activities of Temocapril.Experimental, Investigational
TerlipressinDiazoxide may increase the hypotensive activities of Terlipressin.Approved, Investigational
TetrahydropalmatineDiazoxide may increase the hypotensive activities of Tetrahydropalmatine.Investigational
TheodrenalineDiazoxide may increase the hypotensive activities of Theodrenaline.Investigational
ThiopentalThiopental may increase the hypotensive activities of Diazoxide.Approved, Vet Approved
TiboloneDiazoxide may increase the hypotensive activities of Tibolone.Approved, Investigational
TicrynafenDiazoxide may increase the hypotensive activities of Ticrynafen.Withdrawn
TimololDiazoxide may increase the hypotensive activities of Timolol.Approved
TolazamideThe therapeutic efficacy of Tolazamide can be decreased when used in combination with Diazoxide.Approved
TolazolineDiazoxide may increase the hypotensive activities of Tolazoline.Approved, Vet Approved
TolbutamideThe therapeutic efficacy of Tolbutamide can be decreased when used in combination with Diazoxide.Approved
TolonidineDiazoxide may increase the hypotensive activities of Tolonidine.Experimental
ToloxatoneToloxatone may increase the hypotensive activities of Diazoxide.Approved
TorasemideDiazoxide may increase the hypotensive activities of Torasemide.Approved
TrandolaprilDiazoxide may increase the hypotensive activities of Trandolapril.Approved
Trans-2-PhenylcyclopropylamineTrans-2-Phenylcyclopropylamine may increase the hypotensive activities of Diazoxide.Experimental
TranylcypromineTranylcypromine may increase the hypotensive activities of Diazoxide.Approved
TravoprostDiazoxide may increase the hypotensive activities of Travoprost.Approved
TreprostinilDiazoxide may increase the hypotensive activities of Treprostinil.Approved, Investigational
TrichlormethiazideThe risk or severity of adverse effects can be increased when Trichlormethiazide is combined with Diazoxide.Approved, Vet Approved
TrimazosinDiazoxide may increase the hypotensive activities of Trimazosin.Experimental
TrimethaphanDiazoxide may increase the hypotensive activities of Trimethaphan.Approved, Investigational
TroglitazoneThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Diazoxide.Investigational, Withdrawn
UdenafilUdenafil may increase the antihypertensive activities of Diazoxide.Approved, Investigational
UnoprostoneDiazoxide may increase the hypotensive activities of Unoprostone.Approved
UrapidilDiazoxide may increase the hypotensive activities of Urapidil.Investigational
ValsartanDiazoxide may increase the hypotensive activities of Valsartan.Approved, Investigational
VardenafilVardenafil may increase the antihypertensive activities of Diazoxide.Approved
VildagliptinThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Diazoxide.Approved, Investigational
VincamineDiazoxide may increase the hypotensive activities of Vincamine.Experimental
VinpocetineDiazoxide may increase the hypotensive activities of Vinpocetine.Investigational
VogliboseThe therapeutic efficacy of Voglibose can be decreased when used in combination with Diazoxide.Approved, Investigational
XipamideDiazoxide may increase the hypotensive activities of Xipamide.Experimental
XylometazolineDiazoxide may increase the hypotensive activities of Xylometazoline.Approved
YohimbineYohimbine may decrease the antihypertensive activities of Diazoxide.Approved, Vet Approved
ZofenoprilDiazoxide may increase the hypotensive activities of Zofenopril.Experimental
Food Interactions
Not Available

References

Synthesis Reference

Topliss, J.G., Sperber, N. and Rubin, A.A.; U.S. Patent 2,986,573; May 30, 1961; assigned to Schering Corporation. Topliss, J.G., Sperber, N. and Rubin, A.A.; U.S. Patent 3,345,365; October 3, 1967; assigned to Schering Corporation.

General References
Not Available
External Links
Human Metabolome Database
HMDB15251
KEGG Drug
D00294
KEGG Compound
C06949
PubChem Compound
3019
PubChem Substance
46508027
ChemSpider
2911
BindingDB
86248
ChEBI
4495
ChEMBL
CHEMBL181
Therapeutic Targets Database
DAP000956
PharmGKB
PA449285
IUPHAR
2409
Guide to Pharmacology
GtP Drug Page
HET
20J
Drugs.com
Drugs.com Drug Page
Wikipedia
Diazoxide
ATC Codes
V03AH01 — DiazoxideC02DA01 — DiazoxideG01AE10 — Combinations of sulfonamides
AHFS Codes
  • 24:08.20 — Direct Vasodilators
PDB Entries
4lv9
MSDS
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Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2TerminatedTreatmentDepression1
2CompletedTreatmentBMI >30 kg/m21
2CompletedTreatmentBMI >30 kg/m2 / Hyperinsulinism1
2CompletedTreatmentHypothalamic Obesity1
2RecruitingTreatmentType 2 Diabetes Mellitus1
2, 3Unknown StatusTreatmentHypoglycemia / Infant, Diabetic Mother / Infant, Large for Gestational Age / Infant, Newborn, Diseases / Pregnancy in Diabetics1
3CompletedTreatmentHypothalamic-pituitary Lesions / Postsurgical craniopharyngioma1
4CompletedTreatmentDiabetes, Diabetes Mellitus Type 11
4Unknown StatusPreventionDiabetes, Diabetes Mellitus Type 11
4WithdrawnTreatmentGastro-enteropancreatic Neuroendocrine Tumor1
Not AvailableCompletedScreeningDiabetes Mellitus, Insulin-Dependent / Ischemia-Reperfusion Injury1
Not AvailableCompletedTreatmentPolycystic Ovarian Syndrome1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Dosage forms
FormRouteStrength
LiquidIntravenous15 mg
CapsuleOral100 mg
SuspensionOral50 mg/mL
SuspensionOral50 mg
Prices
Unit descriptionCostUnit
Proglycem 50 mg/ml Suspension 30ml Bottle197.05USD bottle
Diazoxide powder85.07USD g
Proglycem 100 mg Capsule1.65USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)330Topliss, J.G., Sperber, N. and Rubin, A.A.; U.S. Patent 2,986,573; May 30, 1961; assigned to Schering Corporation. Topliss, J.G., Sperber, N. and Rubin, A.A.; U.S. Patent 3,345,365; October 3, 1967; assigned to Schering Corporation.
water solubility2850 mg/LNot Available
logP1.20HANSCH,C ET AL. (1995)
pKa8.74SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.552 mg/mLALOGPS
logP1.09ALOGPS
logP1ChemAxon
logS-2.6ALOGPS
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
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.5923
Caco-2 permeable-0.5765
P-glycoprotein substrateNon-substrate0.6817
P-glycoprotein inhibitor INon-inhibitor0.6924
P-glycoprotein inhibitor IINon-inhibitor0.6927
Renal organic cation transporterNon-inhibitor0.8107
CYP450 2C9 substrateNon-substrate0.5606
CYP450 2D6 substrateNon-substrate0.8064
CYP450 3A4 substrateNon-substrate0.5774
CYP450 1A2 substrateInhibitor0.9108
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.831
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7977
Ames testNon AMES toxic0.7888
CarcinogenicityNon-carcinogens0.8304
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.3408 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9233
hERG inhibition (predictor II)Non-inhibitor0.9271
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-004i-0090000000-e862bca94c5672c9f532
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-004i-0090000000-23cdf34c4eb3479d62ab
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-004i-0590000000-b597fe9df00aeb0e5c42
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-004i-0910000000-2dc8c72c747ff34f5534
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-004i-1900000000-dded4e98b05043368b90
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-03di-0190000000-9f83244458c5cc11c589
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0bu3-1950000000-80f36d9e4aae5c2acf9c
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-004l-6900000000-49c0abb20e85be8d5cdc
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-004i-9200000000-044096d3b3178a811986
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-004i-9000000000-7a02d106750c03894a70
LC-MS/MS Spectrum - LC-ESI-IT , positiveLC-MS/MSsplash10-0a4l-0980000000-1d3e60eb1a3a4d4a314a
MS/MS Spectrum - , positiveLC-MS/MSsplash10-001i-1790000000-6ba824b6749ffd4b177d
MS/MS Spectrum - , positiveLC-MS/MSsplash10-01tc-4900000000-771b855118fab0901dba

Taxonomy

Description
This compound belongs to the class of organic compounds 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Thiadiazines
Sub Class
Benzothiadiazines
Direct Parent
1,2,4-benzothiadiazine-1,1-dioxides
Alternative Parents
Imidolactams / Benzenoids / Aryl chlorides / Organosulfonic acids and derivatives / Azacyclic compounds / Amidines / Organopnictogen compounds / Organochlorides / Organic oxides / Hydrocarbon derivatives
Substituents
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
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
sulfone, organochlorine compound, benzothiadiazine (CHEBI:4495)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inducer
General Function
Voltage-gated 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 ...
Gene Name
KCNJ11
Uniprot ID
Q14654
Uniprot Name
ATP-sensitive inward rectifier potassium channel 11
Molecular Weight
43540.375 Da
References
  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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:12770942]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
Gene Name
CA1
Uniprot ID
P00915
Uniprot Name
Carbonic anhydrase 1
Molecular Weight
28870.0 Da
References
  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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:7681475]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Zinc ion binding
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 in...
Gene Name
CA2
Uniprot ID
P00918
Uniprot Name
Carbonic anhydrase 2
Molecular Weight
29245.895 Da
References
  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. [PubMed: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. [PubMed:8612523]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Other
General Function
Steroid hormone 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 th...
Gene Name
ATP1A1
Uniprot ID
P05023
Uniprot Name
Sodium/potassium-transporting ATPase subunit alpha-1
Molecular Weight
112895.01 Da
References
  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. [PubMed: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. [PubMed: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. [PubMed:17287451]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Other
General Function
Voltage-gated potassium 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 activati...
Gene Name
KCNMA1
Uniprot ID
Q12791
Uniprot Name
Calcium-activated potassium channel subunit alpha-1
Molecular Weight
137558.115 Da
References
  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. [PubMed: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. [PubMed: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. [PubMed:16446048]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Unknown
General Function
Transporter activity
Specific Function
Key mediator of sodium and chloride reabsorption in this nephron segment, accounting for a significant fraction of renal sodium reabsorption.
Gene Name
SLC12A3
Uniprot ID
P55017
Uniprot Name
Solute carrier family 12 member 3
Molecular Weight
113138.04 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed: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. [PubMed:17016423]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Manganese ion binding
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). E...
Gene Name
GLUL
Uniprot ID
P15104
Uniprot Name
Glutamine synthetase
Molecular Weight
42064.15 Da
References
  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. [PubMed:7926271]

Drug created on June 13, 2005 07:24 / Updated on November 19, 2017 20:34