Banner
targets (1) enzymes (1)
for drugs
Identification
Name Acetohexamide
Accession Number DB00414 (APRD00773)
Type small molecule
Groups approved
Description

A sulfonylurea hypoglycemic agent that is metabolized in the liver to 1-hydrohexamide. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Acetohexamid
Brand names
  • Cyclamide
  • Dimelin
  • Dimelor
  • Dymelor
  • Gamadiabet
  • Hypoglicil
  • Metaglucina
  • Minoral
  • Ordimel
  • Tsiklamid
Brand name mixtures Not Available
Categories
  • Hypoglycemic Agents
  • Sulfonylureas
CAS number 968-81-0
Weight Average: 324.395
Monoisotopic: 324.114377828
Chemical Formula C15H20N2O4S
InChI Key InChIKey=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)
Plain Text
IUPAC Name
1-[(4-acetylbenzene)sulfonyl]-3-cyclohexylurea
SMILES
CC(=O)C1=CC=C(C=C1)S(=O)(=O)NC(=O)NC1CCCCC1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Sulfonylureas
Substructures
  • Sulfonylureas
  • Sulfonyls
  • Benzene and Derivatives
  • Ureas and Derivatives
  • Benzenesulfonamides
  • Aromatic compounds
  • Sulfonamides
  • Benzoyl Derivatives
  • Acetophenones and Derivatives
  • Ketones
Pharmacology
Indication Used in the management of diabetes mellitus type 2 (adult-onset).
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. 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 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.
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.
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
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.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Barr laboratories inc
  • Usl pharma inc
  • Watson laboratories inc
  • Eli lilly industries inc
Packagers
Dosage forms Not Available
Prices Not Available
Patents Not Available
Properties
State solid
Melting point 188-190 oC
Experimental Properties
Property Value Source
water solubility 3430 mg/L PhysProp
logP 2.7 PhysProp
logS -2.06 [ADME Research, USCD] PhysProp
Predicted Properties
Property Value Source
water solubility 4.83e-02 g/l ALOGPS
logP 1.72 ALOGPS
logP 1.81 ChemAxon Molconvert
logS -3.83 ALOGPS
pKa 15.77 ChemAxon Molconvert
hydrogen acceptor count 4 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 92.34 ChemAxon Molconvert
rotatable bond count 3 ChemAxon Molconvert
refractivity 82.77 ChemAxon Molconvert
polarizability 33.97 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00219 Link_out
KEGG Compound C06806 Link_out
PubChem Compound 1989 Link_out
PubChem Substance 46505821 Link_out
ChemSpider 1912 Link_out
ChEBI 28052 Link_out
ChEMBL 28052 Link_out
Therapeutic Targets Database DAP000922 Link_out
PharmGKB PA448023 Link_out
Drug Product Database 15598 Link_out
Drugs.com http://www.drugs.com/mtm/acetohexamide.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Acetohexamide Link_out
ATC Codes
  • A10BB31
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Take without regard to meals.
Targets

1. ATP-sensitive inward rectifier potassium channel 1

Pharmacological action: yes
Actions: inhibitor

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 voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. This channel is activated by internal ATP and can be blocked by external barium

Organism class: human
UniProt ID: P48048 Link_out
Gene: KCNJ1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
Enzymes

1. Carbonyl reductase [NADPH] 1

Actions: substrate

Catalyzes the reduction of a wide variety of carbonyl compounds including the antitumor anthracycline antibiotics. Can convert prostaglandin E2 to prostaglandin F2-alpha

UniProt ID: P16152 Link_out
Gene: CBR1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
Comments
Drug created on June 13, 2005 07:24 / Updated on August 03, 2011 09:30

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.