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Identification
NameAcetohexamide
Accession NumberDB00414  (APRD00773)
TypeSmall Molecule
GroupsWithdrawn
Description

A sulfonylurea hypoglycemic agent that is metabolized in the liver to 1-hydrohexamide. Acetohexamide has been discontinued in the US market.

Structure
Thumb
Synonyms
1-((p-Acetylphenyl)sulfonyl)-3-cyclohexylurea
1-[(4-acetylbenzene)sulfonyl]-3-cyclohexylurea 4-acetyl-N-(cyclohexylcarbamoyl)benzenesulfonamide
Acetohexamid
Acetohexamida
Acétohexamide
Acetohexamide
Acetohexamidum
N-(p-Acetylphenylsulfonyl)-N'-cyclohexylurea
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Dimelor Tablet 1843 500mgtablet500 mgoralEli Lilly Canada Inc1963-12-311998-08-04Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AcetohexamideWatson
DimelinShionogi Seiyaku
DymelorLilly
GamadiabetSalvat
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIQGC8W08I6I
CAS number968-81-0
WeightAverage: 324.395
Monoisotopic: 324.114377828
Chemical FormulaC15H20N2O4S
InChI KeyVGZSUPCWNCWDAN-UHFFFAOYSA-N
InChI
InChI=1S/C15H20N2O4S/c1-11(18)12-7-9-14(10-8-12)22(20,21)17-15(19)16-13-5-3-2-4-6-13/h7-10,13H,2-6H2,1H3,(H2,16,17,19)
IUPAC Name
3-(4-acetylbenzenesulfonyl)-1-cyclohexylurea
SMILES
CC(=O)C1=CC=C(C=C1)S(=O)(=O)NC(=O)NC1CCCCC1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzenesulfonamides
Direct ParentBenzenesulfonamides
Alternative Parents
Substituents
  • Benzenesulfonamide
  • Acetophenone
  • Aryl alkyl ketone
  • Aryl ketone
  • Benzoyl
  • Sulfonylurea
  • Cyclohexylamine
  • Aminosulfonyl compound
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • Ketone
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Pharmacology
IndicationUsed in the management of diabetes mellitus type 2 (adult-onset).
PharmacodynamicsAcetohexamide is an intermediate-acting, first-generation oral sulfonylurea. It lowers blood sugar by stimulating the pancreatic beta cells to secrete insulin and by helping the body use insulin efficiently. The pancreas must produce insulin for this medication to work. Acetohexamide has one-third the potency of chlorpropamide, and twice the potency of tolbutamide; however, similar hypoglycemic efficacy occurs with equipotent dosage of sulfonylureas.
Mechanism of actionSulfonylureas such as acetohexamide bind to an ATP-dependent K+ channel on the cell membrane of pancreatic beta cells. This inhibits a tonic, hyperpolarizing outflux of potassium, which causes the electric potential over the membrane to become more positive. This depolarization opens voltage-gated Ca2+ channels. The rise in intracellular calcium leads to increased fusion of insulin granulae with the cell membrane, and therefore increased secretion of (pro)insulin.
Related Articles
AbsorptionRapidly absorbed from the GI tract.
Volume of distributionNot Available
Protein binding90%
Metabolism

Extensively metabolized in the liver to the active metabolite hydroxyhexamide, which exhibits greater hypoglycemic potency than acetohexamide. Hydroxyhexamide is believed to be responsible for prolonged hypoglycemic effects.

SubstrateEnzymesProduct
Acetohexamide
Not Available
HydroxyhexamideDetails
Route of eliminationNot Available
Half lifeElimination half-life of the parent compound is 1.3 hours and the elimination half-life of the active metabolite is approximately 5-6 hours.
ClearanceNot Available
ToxicityOral, rat LD50: 5 gm/kg; Oral, mouse LD50: >2500 mg/kg. Symptoms of an acetohexamide overdose include hunger, nausea, anxiety, cold sweats, weakness, drowsiness, unconsciousness, and coma.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9425
Blood Brain Barrier+0.8308
Caco-2 permeable-0.6272
P-glycoprotein substrateNon-substrate0.6406
P-glycoprotein inhibitor INon-inhibitor0.8731
P-glycoprotein inhibitor IINon-inhibitor0.8808
Renal organic cation transporterNon-inhibitor0.8538
CYP450 2C9 substrateSubstrate0.6473
CYP450 2D6 substrateNon-substrate0.8795
CYP450 3A4 substrateNon-substrate0.7171
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5913
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.8447
BiodegradationNot ready biodegradable0.8033
Rat acute toxicity2.1793 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8799
hERG inhibition (predictor II)Non-inhibitor0.8982
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Barr laboratories inc
  • Usl pharma inc
  • Watson laboratories inc
  • Eli lilly industries inc
Packagers
Dosage forms
FormRouteStrength
Tabletoral500 mg
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point188-190 °CSigal,M.V.,Jr.andVanArendonk,A.M.; US.Patent3,320,312;May16,1967;assigned to Eli Lilly and Company.
water solubility3430 mg/L (at 37 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP2.44SANGSTER (1993)
logS-2.06ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.0483 mg/mLALOGPS
logP1.72ALOGPS
logP1.81ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)4.31ChemAxon
pKa (Strongest Basic)-7.4ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area92.34 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity82.77 m3·mol-1ChemAxon
Polarizability33.97 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesA10BB31
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AripiprazoleThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Aripiprazole.
Arsenic trioxideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Arsenic trioxide.
ArticaineThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Articaine.
AsenapineThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Asenapine.
AtazanavirThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Atazanavir.
BendroflumethiazideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Bendroflumethiazide.
BetamethasoneThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Betamethasone.
BrexpiprazoleThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Brexpiprazole.
BumetanideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Bumetanide.
BuserelinThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Buserelin.
CeritinibThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Ceritinib.
ChlorothiazideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Chlorothiazide.
ChlorpropamideAcetohexamide may increase the hypoglycemic activities of Chlorpropamide.
ChlorthalidoneThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Chlorthalidone.
ClozapineThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Clozapine.
CorticotropinThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Corticotropin.
Cortisone acetateThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Cortisone acetate.
Cyproterone acetateThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Cyproterone acetate.
DabrafenibThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Dabrafenib.
DanazolThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Danazol.
DarunavirThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Darunavir.
DesogestrelThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Desogestrel.
DexamethasoneThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Dexamethasone.
DiazoxideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Diazoxide.
DienogestThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Dienogest.
DisopyramideAcetohexamide may increase the hypoglycemic activities of Disopyramide.
DrospirenoneThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Drospirenone.
EpinephrineThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Epinephrine.
ErythromycinAcetohexamide may increase the hypoglycemic activities of Erythromycin.
EstradiolThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Estradiol.
Estrone sulfateThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Estropipate.
Etacrynic acidThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Ethacrynic acid.
Ethinyl EstradiolThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Ethinyl Estradiol.
Ethynodiol diacetateThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Ethynodiol.
EtonogestrelThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Etonogestrel.
EverolimusThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Everolimus.
FludrocortisoneThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Fludrocortisone.
FosamprenavirThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Fosamprenavir.
FurosemideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Furosemide.
GliclazideAcetohexamide may increase the hypoglycemic activities of Gliclazide.
GlimepirideAcetohexamide may increase the hypoglycemic activities of Glimepiride.
GlipizideAcetohexamide may increase the hypoglycemic activities of Glipizide.
GlyburideAcetohexamide may increase the hypoglycemic activities of Glyburide.
GoserelinThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Goserelin.
HistrelinThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Histrelin.
HydrochlorothiazideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Hydrochlorothiazide.
HydrocortisoneThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Hydrocortisone.
Hydroxyprogesterone caproateThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Hydroxyprogesterone caproate.
IloperidoneThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Iloperidone.
IndapamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Indapamide.
IndinavirThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Indinavir.
Insulin AspartAcetohexamide may increase the hypoglycemic activities of Insulin Aspart.
Insulin DegludecAcetohexamide may increase the hypoglycemic activities of Insulin degludec.
Insulin DetemirAcetohexamide may increase the hypoglycemic activities of Insulin Detemir.
Insulin GlargineAcetohexamide may increase the hypoglycemic activities of Insulin Glargine.
Insulin GlulisineAcetohexamide may increase the hypoglycemic activities of Insulin Glulisine.
Insulin HumanAcetohexamide may increase the hypoglycemic activities of Insulin Regular.
Insulin LisproAcetohexamide may increase the hypoglycemic activities of Insulin Lispro.
LanreotideAcetohexamide may increase the hypoglycemic activities of Lanreotide.
LeuprolideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Leuprolide.
LevonorgestrelThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Levonorgestrel.
LopinavirThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Lopinavir.
LurasidoneThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Lurasidone.
MecaserminAcetohexamide may increase the hypoglycemic activities of Mecasermin.
Medroxyprogesterone acetateThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Medroxyprogesterone Acetate.
Megestrol acetateThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Megestrol acetate.
MestranolThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Mestranol.
MethotrimeprazineThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Methotrimeprazine.
MethyclothiazideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Methyclothiazide.
MethylprednisoloneThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Methylprednisolone.
MetolazoneThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Metolazone.
MifepristoneAcetohexamide may increase the hypoglycemic activities of Mifepristone.
NadololThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Nadolol.
NateglinideAcetohexamide may increase the hypoglycemic activities of Nateglinide.
NelfinavirThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Nelfinavir.
NiacinThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Niacin.
NilotinibThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Nilotinib.
NorethisteroneThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Norethindrone.
NorgestimateThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Norgestimate.
OctreotideAcetohexamide may increase the hypoglycemic activities of Octreotide.
OlanzapineThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Olanzapine.
PaliperidoneThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Paliperidone.
PasireotideAcetohexamide may increase the hypoglycemic activities of Pasireotide.
PentamidineAcetohexamide may increase the hypoglycemic activities of Pentamidine.
PipotiazineThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Pipotiazine.
PrednisoloneThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Prednisolone.
PrednisoneThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Prednisone.
ProgesteroneThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Progesterone.
QuetiapineThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Quetiapine.
QuinineAcetohexamide may increase the hypoglycemic activities of Quinine.
RepaglinideAcetohexamide may increase the hypoglycemic activities of Repaglinide.
Repository corticotropinThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Repository corticotropin.
RisperidoneThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Risperidone.
RitonavirThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Ritonavir.
SaquinavirThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Saquinavir.
SirolimusThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Sirolimus.
SulfadiazineAcetohexamide may increase the hypoglycemic activities of Sulfadiazine.
SulfamethoxazoleAcetohexamide may increase the hypoglycemic activities of Sulfamethoxazole.
SulfisoxazoleAcetohexamide may increase the hypoglycemic activities of Sulfisoxazole.
SunitinibAcetohexamide may increase the hypoglycemic activities of Sunitinib.
TacrolimusThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Tacrolimus.
TemsirolimusThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Temsirolimus.
TipranavirThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Tipranavir.
TolazamideAcetohexamide may increase the hypoglycemic activities of Tolazamide.
TolbutamideAcetohexamide may increase the hypoglycemic activities of Tolbutamide.
TorasemideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Torasemide.
TriamcinoloneThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Triamcinolone.
TrimethoprimAcetohexamide may increase the hypoglycemic activities of Trimethoprim.
TriptorelinThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Triptorelin.
VorinostatThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Vorinostat.
ZiprasidoneThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Ziprasidone.
Food Interactions
  • Avoid alcohol.
  • Take without regard to meals.

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Phosphatidylinositol-4,5-bisphosphate binding
Specific Function:
In the kidney, probably plays a major role in potassium homeostasis. 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 vol...
Gene Name:
KCNJ1
Uniprot ID:
P48048
Molecular Weight:
44794.6 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
substrate
General Function:
Prostaglandin-e2 9-reductase activity
Specific Function:
NADPH-dependent reductase with broad substrate specificity. Catalyzes the reduction of a wide variety of carbonyl compounds including quinones, prostaglandins, menadione, plus various xenobiotics. Catalyzes the reduction of the antitumor anthracyclines doxorubicin and daunorubicin to the cardiotoxic compounds doxorubicinol and daunorubicinol. Can convert prostaglandin E2 to prostaglandin F2-alp...
Gene Name:
CBR1
Uniprot ID:
P16152
Molecular Weight:
30374.73 Da
References
  1. Imamura Y, Shimada H: Differential pharmacokinetics of acetohexamide in male Wistar-Imamichi and Sprague-Dawley rats: role of microsomal carbonyl reductase. Biol Pharm Bull. 2005 Jan;28(1):185-7. [PubMed:15635190 ]
  2. Imamura Y, Koga T, Higuchi T, Otagiri M, Sugino E, Hibino S: Inhibitory effect of drugs with a ketone group on reduction of acetohexamide catalyzed by carbonyl reductase from rabbit kidney. J Enzyme Inhib. 1997 Feb;11(4):285-92. [PubMed:9208371 ]
  3. Kishimoto M, Kawamori R, Kamada T, Inaba T: Carbonyl reductase activity for acetohexamide in human erythrocytes. Drug Metab Dispos. 1994 May-Jun;22(3):367-70. [PubMed:8070312 ]
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Drug created on June 13, 2005 07:24 / Updated on September 29, 2015 11:48