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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
Salts Not Available
Brand names
Name Company
Cyclamide
Dimelin
Dimelor
Dymelor
Gamadiabet
Hypoglicil
Metaglucina
Minoral
Ordimel
Tsiklamid
Brand 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.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Acetohexamide
    		Hydroxyhexamide Details
    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
    Experimental Properties
    Property Value Source
    melting point 188-190 °C Not Available
    water solubility 3430 mg/L (at 37 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992)
    logP 2.44 SANGSTER (1993)
    logS -2.06 ADME Research, USCD
    Predicted Properties
    Property Value Source
    water solubility 4.83e-02 g/l ALOGPS
    logP 1.72 ALOGPS
    logP 1.81 ChemAxon
    logS -3.8 ALOGPS
    pKa (strongest acidic) 4.31 ChemAxon
    pKa (strongest basic) -7.4 ChemAxon
    physiological charge -1 ChemAxon
    hydrogen acceptor count 4 ChemAxon
    hydrogen donor count 2 ChemAxon
    polar surface area 92.34 ChemAxon
    rotatable bond count 3 ChemAxon
    refractivity 82.77 ChemAxon
    polarizability 33.97 ChemAxon
    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 PA164777011 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
    Drug Interaction
    Acebutolol Acebutolol may decrease symptoms of hypoglycemia and increase the time required for the body to compensate for hypoglycemia.
    Acetylsalicylic acid Acetylsalicylic acid increases the effect of sulfonylurea, acetohexamide.
    Atenolol The beta-blocker, atenolol, may decrease symptoms of hypoglycemia.
    Betaxolol The beta-blocker, betaxolol, may decrease symptoms of hypoglycemia.
    Bisoprolol The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.
    Carteolol The beta-blocker, carteolol, may decrease symptoms of hypoglycemia.
    Carvedilol The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
    Chloramphenicol Chloramphenicol may increase the effect of sulfonylurea, acetohexamide.
    Clofibrate Clofibrate may increase the effect of sulfonylurea, acetohexamide.
    Dicumarol Dicumarol may increase the effect of sulfonylurea, acetohexamide.
    Esmolol The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.
    Labetalol The beta-blocker, labetalol, may decrease symptoms of hypoglycemia.
    Metoprolol The beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.
    Nadolol The beta-blocker, nadolol, may decrease symptoms of hypoglycemia.
    Oxprenolol The beta-blocker, oxprenolol, may decrease symptoms of hypoglycemia.
    Phenylbutazone Phenylbutazone may increase the effect of acetohexamide.
    Pindolol The beta-blocker, pindolol, may decrease symptoms of hypoglycemia.
    Practolol The beta-blocker, practolol, may decrease symptoms of hypoglycemia.
    Propranolol The beta-blocker, propranolol, may decrease symptoms of hypoglycemia.
    Rifampin Rifampin may decrease the effect of sulfonylurea, acetohexamide.
    Sotalol The beta-blocker, sotalol, may decrease symptoms of hypoglycemia.
    Timolol The beta-blocker, timolol, may decrease symptoms of hypoglycemia.
    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 February 08, 2013 16:19