NAV

Acetohexamide

Identification

Generic Name
Acetohexamide
DrugBank Accession Number
DB00414
Background

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

Type
Small Molecule
Groups
Approved, Investigational, Withdrawn
Structure
3D
Similar Structures
Weight
Average: 324.395
Monoisotopic: 324.114377828
Chemical Formula
C15H20N2O4S
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 IDs
  • 33006
Poor quality drug data slowing you down?
Unlock 38% more drug discovery time and eliminate decision-making doubts with this one-stop guide to quality drug data.
Download eBook
Poor quality drug data slowing you down?
Download eBook

Pharmacology

Indication

Used in the management of diabetes mellitus type 2 (adult-onset).

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

Acetohexamide 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. Due to its primary action on the pancreatic beta cells, the drug is only effective when there are functional pancreatic beta cells that can produce insulin granules. 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 action

Sulfonylureas 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.

TargetActionsOrganism
AATP-sensitive inward rectifier potassium channel 1
inhibitor
Humans
Absorption

Rapidly absorbed from the GI tract.

Volume of distribution

Not Available

Protein binding

90%

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.

Hover over products below to view reaction partners

Route of elimination

Not Available

Half-life

Elimination half-life of the parent compound is 1.3 hours and the elimination half-life of the active metabolite is approximately 5-6 hours.

Clearance

Not Available

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

Oral, 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.

Pathways
Not Available
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
Integrate drug-drug
interactions in your software
AbataceptThe metabolism of Acetohexamide can be increased when combined with Abatacept.
AbrocitinibThe metabolism of Abrocitinib can be decreased when combined with Acetohexamide.
AcarboseThe risk or severity of hypoglycemia can be increased when Acarbose is combined with Acetohexamide.
AcebutololThe therapeutic efficacy of Acetohexamide can be increased when used in combination with Acebutolol.
AceclofenacThe protein binding of Acetohexamide can be decreased when combined with Aceclofenac.
Food Interactions
  • Avoid alcohol.
  • Take with or without food. The absorption is unaffected by food.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
International/Other Brands
Acetohexamide (Watson) / Dimelin (Shionogi Seiyaku) / Dymelor (Lilly) / Gamadiabet (Salvat)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Dimelor Tablet 1843 500mgTablet500 mg / tabOralEli Lilly & Co. Ltd.1963-12-311998-08-04Canada flag

Categories

ATC Codes
G01AE10 — Combinations of sulfonamidesA10BB31 — Acetohexamide
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as alkyl-phenylketones. These are aromatic compounds containing a ketone substituted by one alkyl group, and a phenyl group.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbonyl compounds
Direct Parent
Alkyl-phenylketones
Alternative Parents
Benzenesulfonamides / Benzenesulfonyl compounds / Acetophenones / Benzoyl derivatives / Aryl alkyl ketones / Sulfonylureas / Organosulfonic acids and derivatives / Aminosulfonyl compounds / Propargyl-type 1,3-dipolar organic compounds / Carboximidic acids and derivatives
show 3 more
Substituents
Acetophenone / Alkyl-phenylketone / Aminosulfonyl compound / Aromatic homomonocyclic compound / Aryl alkyl ketone / Benzenesulfonamide / Benzenesulfonyl group / Benzenoid / Benzoyl / Carboximidic acid derivative
show 13 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
N-sulfonylurea, acetophenones (CHEBI:28052)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
QGC8W08I6I
CAS number
968-81-0
InChI Key
VGZSUPCWNCWDAN-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
1-(4-acetylbenzenesulfonyl)-3-cyclohexylurea
SMILES
CC(=O)C1=CC=C(C=C1)S(=O)(=O)NC(=O)NC1CCCCC1

References

General References
Not Available
Human Metabolome Database
HMDB0014558
KEGG Drug
D00219
KEGG Compound
C06806
PubChem Compound
1989
PubChem Substance
46505821
ChemSpider
1912
RxNav
173
ChEBI
28052
ChEMBL
CHEMBL1589
ZINC
ZINC000018067894
Therapeutic Targets Database
DAP000922
PharmGKB
PA164777011
Drugs.com
Drugs.com Drug Page
Wikipedia
Acetohexamide

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
2CompletedTreatmentImpaired Glucose Tolerance / Type 2 Diabetes Mellitus1
Not AvailableCompletedNot AvailableType 2 Diabetes Mellitus3

Pharmacoeconomics

Manufacturers
  • Barr laboratories inc
  • Usl pharma inc
  • Watson laboratories inc
  • Eli lilly industries inc
Packagers
  • Barr Pharmaceuticals
  • Murfreesboro Pharmaceutical Nursing Supply
Dosage Forms
FormRouteStrength
TabletOral
TabletOral500 mg / tab
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)188-190 °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 RuleNoChemaxon
MDDR-like RuleNoChemaxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-001i-9762000000-4ab556868f4c484f31f6
GC-MS Spectrum - EI-BGC-MSsplash10-03di-8390000000-581eca2d35a4f5f0362a
GC-MS Spectrum - EI-BGC-MSsplash10-0a5c-9200000000-09e03cfa3bf5df8c2b45
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-001i-2944000000-abefa81ad579a339c974
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0002-0901000000-fac5f231fdd89589f869
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0159-0910000000-8f70feff0019f50f369f
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0002-1900000000-23419a7d61ce65e71afd
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-9330000000-a5c02eff2e91db7d588a
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0w33-2790000000-4d609585b6b6edde1e42
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-190.6097
predicted
DarkChem Lite v0.1.0
[M-H]-177.3457124
predicted
DarkChem Lite v0.1.0
[M-H]-190.8133
predicted
DarkChem Lite v0.1.0
[M-H]-170.24959
predicted
DeepCCS 1.0 (2019)
[M+H]+192.1965
predicted
DarkChem Lite v0.1.0
[M+H]+184.3668994
predicted
DarkChem Lite v0.1.0
[M+H]+190.9431
predicted
DarkChem Lite v0.1.0
[M+H]+172.6452
predicted
DeepCCS 1.0 (2019)
[M+Na]+191.0533
predicted
DarkChem Lite v0.1.0
[M+Na]+195.1728
predicted
DarkChem Lite v0.1.0
[M+Na]+178.83746
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Details1. ATP-sensitive inward rectifier potassium channel 1
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
Curator comments
This target action is based on the drug class of sulfonylureas.
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...
Gene Name
KCNJ1
Uniprot ID
P48048
Uniprot Name
ATP-sensitive inward rectifier potassium channel 1
Molecular Weight
44794.6 Da
References
  1. Tanemoto M, Vanoye CG, Dong K, Welch R, Abe T, Hebert SC, Xu JZ: Rat homolog of sulfonylurea receptor 2B determines glibenclamide sensitivity of ROMK2 in Xenopus laevis oocyte. Am J Physiol Renal Physiol. 2000 Apr;278(4):F659-66. doi: 10.1152/ajprenal.2000.278.4.F659. [Article]
  2. Bednarczyk P, Kicinska A, Laskowski M, Kulawiak B, Kampa R, Walewska A, Krajewska M, Jarmuszkiewicz W, Szewczyk A: Evidence for a mitochondrial ATP-regulated potassium channel in human dermal fibroblasts. Biochim Biophys Acta Bioenerg. 2018 May;1859(5):309-318. doi: 10.1016/j.bbabio.2018.02.005. Epub 2018 Feb 16. [Article]
  3. Konstas AA, Dabrowski M, Korbmacher C, Tucker SJ: Intrinsic sensitivity of Kir1.1 (ROMK) to glibenclamide in the absence of SUR2B. Implications for the identity of the renal ATP-regulated secretory K+ channel. J Biol Chem. 2002 Jun 14;277(24):21346-51. doi: 10.1074/jbc.M202005200. Epub 2002 Apr 1. [Article]

Enzymes

Details1. Cytochrome P450 2C9
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. May M, Schindler C: Clinically and pharmacologically relevant interactions of antidiabetic drugs. Ther Adv Endocrinol Metab. 2016 Apr;7(2):69-83. doi: 10.1177/2042018816638050. Epub 2016 Mar 31. [Article]
Details2. Carbonyl reductase [NADPH] 1
Kind
Protein
Organism
Humans
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. ...
Gene Name
CBR1
Uniprot ID
P16152
Uniprot Name
Carbonyl reductase [NADPH] 1
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. [Article]
  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. [Article]
  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. [Article]

Carriers

Details1. Serum albumin
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Joseph KS, Hage DS: Characterization of the binding of sulfonylurea drugs to HSA by high-performance affinity chromatography. J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Jun 1;878(19):1590-8. doi: 10.1016/j.jchromb.2010.04.019. [Article]
  2. Joseph KS, Anguizola J, Jackson AJ, Hage DS: Chromatographic analysis of acetohexamide binding to glycated human serum albumin. J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Oct 15;878(28):2775-81. doi: 10.1016/j.jchromb.2010.08.021. Epub 2010 Aug 21. [Article]
  3. Yoo MJ, Hage DS: Use of peak decay analysis and affinity microcolumns containing silica monoliths for rapid determination of drug-protein dissociation rates. J Chromatogr A. 2011 Apr 15;1218(15):2072-8. doi: 10.1016/j.chroma.2010.09.070. Epub 2010 Oct 16. [Article]
  4. Basiaga SB, Hage DS: Chromatographic studies of changes in binding of sulfonylurea drugs to human serum albumin due to glycation and fatty acids. J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Nov 15;878(30):3193-7. doi: 10.1016/j.jchromb.2010.09.033. Epub 2010 Oct 23. [Article]
  5. Tong Z, Joseph KS, Hage DS: Detection of heterogeneous drug-protein binding by frontal analysis and high-performance affinity chromatography. J Chromatogr A. 2011 Dec 9;1218(49):8915-24. doi: 10.1016/j.chroma.2011.04.078. Epub 2011 May 6. [Article]

Drug created at June 13, 2005 13:24 / Updated at November 03, 2023 23:41