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Showing drug card for Acetohexamide (DB00414)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:05:50
Primary Accession Number DB00414
Secondary Accession Number
  • APRD00773
Name Acetohexamide
Drug Type
  • Approved
  • Small Molecule
Description A sulfonylurea hypoglycemic agent that is metabolized in the liver to 1-hydrohexamide. [PubChem]
Synonyms
  1. Acetohexamid
Brand Names
  1. Cyclamide
  2. Dimelin
  3. Dimelor
  4. Dymelor
  5. Gamadiabet
  6. Hypoglicil
  7. Metaglucina
  8. Minoral
  9. Ordimel
  10. Tsiklamid
Brand Mixtures Not Available
Chemical IUPAC Name 3-(4-acetylphenyl)sulfonyl-1-cyclohexylurea
Chemical Formula C15H20N2O4S
Chemical Structure Structure
CAS Registry Number 968-81-0
InChI Identifier InChI=1/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)/f/h16-17H
InChI Key VGZSUPCWNCWDAN-XQMQJMAZCC
KEGG Drug D00219 Link Image
KEGG Compound C06806 Link Image
PubChem Compound 1989 Link Image
PubChem Substance 9025 Link Image
ChEBI ID 28052 Link Image
PharmGKB ID PA448023 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 00015598 Link Image
RxList Link Not Available
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Acetohexamide Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference Not Available
Average Molecular Weight 324.3950
Monoisotopic Molecular Weight 324.1144
State Solid
Melting Point 188-190 oC
Experimental Water Solubility 3430 mg/L Source: PhysProp
Predicted Water Solubility 4.83e-02 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 2.7 Source: PhysProp
Predicted LogP 1.72 Calculated using ALOGPS
Experimental LogS -2.06 [ADME Research, USCD]
Predicted LogS -3.83 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES CC(=O)C1=CC=C(C=C1)S(=O)(=O)NC(=O)NC1CCCCC1
Canonical SMILES CC(=O)C1=CC=C(C=C1)S(=O)(=O)NC(=O)NC1CCCCC1
Drug Category
  • Hypoglycemic Agents
  • Sulfonylureas
ATC Codes
AHFS Codes Not Available
Indication Used in the management of diabetes mellitus type 2 (adult-onset).
Pharmacology 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.
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.
Protein Binding 90%
Biotransformation 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.
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.
Dosage Forms Not Available
Patient Information Not Available
Contraindications Show Link Image
Interactions Not Available
Drug Interactions
Drug Interaction
Acebutolol The beta-blocker decreases the symptoms of hypoglycemia
Aspirin The salicylate increases the effect of sulfonylurea
Atenolol The beta-blocker decreases the symptoms of hypoglycemia
Betaxolol The beta-blocker decreases the symptoms of hypoglycemia
Bevantolol The beta-blocker decreases the symptoms of hypoglycemia
Bisoprolol The beta-blocker decreases the symptoms of hypoglycemia
Carteolol The beta-blocker decreases the symptoms of hypoglycemia
Carvedilol The beta-blocker decreases the symptoms of hypoglycemia
Chloramphenicol The agent increases the effect of sulfonylurea
Clofibrate The agent increases the effect of sulfonylurea
Diazoxide Diazoxide / sulfonylurea:Antagonism of action
Dicumarol The agent increases the effect of sulfonylurea
Dicumarol The agent increases the effect of sulfonylurea
Esmolol The beta-blocker decreases the symptoms of hypoglycemia
Glucosamine Possible hyperglycemia
Isocarboxazid The MAO inhibitor increases the effect of the hypoglycemic agent
Labetalol The beta-blocker decreases the symptoms of hypoglycemia
Metoprolol The beta-blocker decreases the symptoms of hypoglycemia
Nadolol The beta-blocker decreases the symptoms of hypoglycemia
Phenelzine The MAO inhibitor increases the effect of the hypoglycemic agent
Phenylbutazone Increases the effect of the hypoglycemic agent
Pindolol The beta-blocker decreases the symptoms of hypoglycemia
Practolol The beta-blocker decreases the symptoms of hypoglycemia
Propranolol The beta-blocker decreases the symptoms of hypoglycemia
Repaglinide Similar mode of action - questionable association
Rifampin Rifampin decreases the effect of sulfonylurea
Salicyclic acid The salicylate increases the effect of sulfonylurea
Sotalol The beta-blocker decreases the symptoms of hypoglycemia
Sulfacytine Sulfonamide/sulfonylurea: possible hypoglycemia
Sulfadiazine Sulfonamide/Sulfonylurea - possible hypoglycemia
Sulfadoxine Sulfonamide/sulfonylurea: possible hypoglycemia
Sulfamethizole Sulfonamide/Sulfonylurea - possible hypoglycemia
Sulfamethoxazole Sulfonamide/Sulfonylurea - possible hypoglycemia
Sulfapyridine Sulfonamide/Sulfonylurea - possible hypoglycemia
Sulfasalazine Sulfonamide/Sulfonylurea - possible hypoglycemia
Sulfisoxazole Sulfonamide/Sulfonylurea - possible hypoglycemia
Timolol The beta-blocker decreases the symptoms of hypoglycemia
Tranylcypromine The MAO inhibitor increases the effect of the hypoglycemic agent
Food Interactions
  • Avoid alcohol.
  • Take without regard to meals.
Pathways Not Available
General References
  1. Drugs.com Link Image
  2. Wikipedia Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Carbonyl reductase [NADPH] 1
Targets
  1. ATP-sensitive inward rectifier potassium channel 1
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Carbonyl reductase [NADPH] 1
Enzyme 1 Gene Name CBR1
Enzyme 1 SwissProt ID P16152 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P16152|DHCA_HUMAN Carbonyl reductase [NADPH] 1 
SSGIHVALVTGGNKGIGLAIVRDLCRLFSGDVVLTARDVTRGQAAVQQLQAEGLSPRFHQ
LDIDDLQSIRALRDFLRKEYGGLDVLVNNAGIAFKVADPTPFHIQAEVTMKTNFFGTRDV
CTELLPLIKPQGRVVNVSSIMSVRALKSCSPELQQKFRSETITEEELVGLMNKFVEDTKK
GVHQKEGWPSSAYGVTKIGVTVLSRIHARKLSEQRKGDKILLNACCPGWVRTDMAGPKAT
KSPEEGAETPVYLALLPPDAEGPHGQFVSEKRVEQW
Drug Target 1 [top]
Target 1 ID 709
Target 1 Name ATP-sensitive inward rectifier potassium channel 1
Target 1 Synonyms
  1. ATP-regulated potassium channel ROM-K
  2. Kir1.1
  3. Potassium channel, inwardly rectifying subfamily J member 1
Target 1 Gene Name KCNJ1
Target 1 Protein Sequence >ATP-sensitive inward rectifier potassium channel 1 
MNASSRNVFDTLIRVLTESMFKHLRKWVVTRFFGHSRQRARLVSKDGRCNIEFGNVEAQS
RFIFFVDIWTTVLDLKWRYKMTIFITAFLGSWFFFGLLWYAVAYIHKDLPEFHPSANHTP
CVENINGLTSAFLFSLETQVTIGYGFRCVTEQCATAIFLLIFQSILGVIINSFMCGAILA
KISRPKKRAKTITFSKNAVISKRGGKLCLLIRVANLRKSLLIGSHIYGKLLKTTVTPEGE
TIILDQININFVVDAGNENLFFISPLTIYHVIDHNSPFFHMAAETLLQQDFELVVFLDGT
VESTSATCQVRTSYVPEEVLWGYRFAPIVSKTKEGKYRVDFHNFSKTVEVETPHCAMCLY
NEKDVRARMKRGYDNPNFILSEVNETDDTKM
Target 1 Number of Residues 397
Target 1 Molecular Weight 44795
Target 1 Theoretical pI 9.04
Target 1 GO Classification
Function
transporter activity
ion transporter activity
ion channel activity
voltage-gated ion channel activity
voltage-gated potassium channel activity
inward rectifier potassium channel activity
Process
physiological process
cellular physiological process
transport
ion transport
cation transport
monovalent inorganic cation transport
potassium ion transport
Component
cell
membrane
Target 1 General Function Involved in inward rectifier potassium channel activity
Target 1 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 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
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 78-102
  • 156-177
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 529313 Link Image
Target 1 UniProtKB/Swiss-Prot ID P48048 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name IRK1_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 1 Gene Sequence >1176 bp 
ATGAATGCTTCCAGTCGGAATGTGTTTGACACGTTGATCAGGGTGTTGACAGAAAGTATG
TTCAAACATCTTCGGAAATGGGTCGTCACTCGCTTTTTTGGGCATTCTCGGCAAAGAGCA
AGGCTAGTCTCCAAAGATGGAAGGTGCAACATAGAATTTGGCAATGTGGAGGCACAGTCA
AGGTTTATATTCTTTGTGGACATCTGGACAACGGTACTTGACCTCAAGTGGAGATACAAA
ATGACCATTTTCATCACAGCCTTCTTGGGGAGTTGGTTTTTCTTTGGTCTCCTGTGGTAT
GCAGTAGCGTACATTCACAAAGACCTCCCGGAATTCCATCCTTCTGCCAATCACACTCCC
TGTGTGGAGAATATTAATGGCTTGACCTCAGCTTTTCTGTTTTCTCTGGAGACTCAAGTG
ACCATTGGATATGGATTCAGGTGTGTGACAGAACAGTGTGCCACTGCCATTTTTCTGCTT
ATCTTTCAGTCTATACTTGGAGTTATAATCAATTCTTTCATGTGTGGGGCCATCTTAGCC
AAGATCTCCAGGCCCAAAAAACGTGCCAAGACCATTACGTTCAGCAAGAACGCAGTGATC
AGCAAACGGGGAGGGAAGCTTTGCCTCCTAATCCGAGTGGCTAATCTCAGGAAGAGCCTT
CTTATTGGCAGTCACATTTATGGAAAGCTTCTGAAGACCACAGTCACTCCTGAAGGAGAG
ACCATTATTTTGGACCAGATCAATATCAACTTTGTAGTTGACGCTGGGAATGAAAATTTA
TTCTTCATCTCCCCATTGACAATTTACCATGTCATTGATCACAACAGCCCTTTCTTCCAC
ATGGCAGCGGAGACCCTTCTCCAGCAGGACTTTGAATTAGTGGTGTTTTTAGATGGCACA
GTGGAGTCCACCAGTGCTACCTGCCAAGTCCGGACATCCTATGTCCCAGAGGAGGTGCTT
TGGGGCTACCGTTTTGCTCCCATAGTATCCAAGACAAAGGAAGGGAAATACCGAGTGGAT
TTCCATAACTTTAGCAAGACAGTGGAAGTGGAGACCCCTCACTGTGCCATGTGCCTTTAT
AATGAGAAAGATGTTAGAGCCAGGATGAAGAGAGGCTATGACAACCCCAACTTCATCTTG
TCAGAAGTCAATGAAACAGATGACACCAAAATGTAA
Target 1 GenBank Gene ID
Target 1 GeneCard ID KCNJ1 Link Image
Target 1 GenAtlas ID KCNJ1 Link Image
Target 1 HGNC ID HGNC:6255 Link Image
Target 1 Chromosome Location 11
Target 1 Locus 11q24
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Krishnan SN, Desai T, Ward DC, Haddad GG: Isolation and chromosomal localization of a human ATP-regulated potassium channel. Hum Genet. 1995 Aug;96(2):155-60. [PubMed Link Image]
  2. Shuck ME, Bock JH, Benjamin CW, Tsai TD, Lee KS, Slightom JL, Bienkowski MJ: Cloning and characterization of multiple forms of the human kidney ROM-K potassium channel. J Biol Chem. 1994 Sep 30;269(39):24261-70. [PubMed Link Image]
  3. Yano H, Philipson LH, Kugler JL, Tokuyama Y, Davis EM, Le Beau MM, Nelson DJ, Bell GI, Takeda J: Alternative splicing of human inwardly rectifying K+ channel ROMK1 mRNA. Mol Pharmacol. 1994 May;45(5):854-60. [PubMed Link Image]
  4. Mutations in the gene encoding the inwardly-rectifying renal potassium channel, ROMK, cause the antenatal variant of Bartter syndrome: evidence for genetic heterogeneity. International Collaborative Study Group for Bartter-like Syndromes. Hum Mol Genet. 1997 Jan;6(1):17-26. [PubMed Link Image]
Target 1 Drug References
  1. 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 Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]

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.