| 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 |
|
| Name |
Acetohexamide |
| Drug Type |
|
| Description |
A sulfonylurea hypoglycemic agent that is metabolized in the liver to 1-hydrohexamide. [PubChem] |
| Synonyms |
- Acetohexamid
|
| Brand Names |
- Cyclamide
- Dimelin
- Dimelor
- Dymelor
- Gamadiabet
- Hypoglicil
- Metaglucina
- Minoral
- Ordimel
- Tsiklamid
|
| Brand Mixtures |
Not Available |
| Chemical IUPAC Name |
3-(4-acetylphenyl)sulfonyl-1-cyclohexylurea |
| Chemical Formula |
C15H20N2O4S |
| Chemical 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  |
| KEGG Compound |
C06806  |
| PubChem Compound |
1989  |
| PubChem Substance |
9025  |
| ChEBI ID |
28052  |
| PharmGKB ID |
PA448023  |
| HET ID |
Not Available |
| GenBank ID |
Not Available |
| Drug ID Number [DIN] |
00015598  |
| RxList Link |
Not Available |
| PDRhealth Link |
Not Available |
| Wikipedia Link |
http://en.wikipedia.org/wiki/Acetohexamide  |
| 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 | Download  |
| SDF File |
Show | Download  |
| PDB File |
Show | Download  |
| 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  |
| 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 |
- Drugs.com

- Wikipedia

|
| Organisms Affected |
|
| Phase 1 Metabolizing Enzymes |
- Carbonyl reductase [NADPH] 1
|
| Targets |
- ATP-sensitive inward rectifier potassium channel 1
|
|
Drug Target 1
[top]
|
| Target 1 ID |
709 |
| Target 1 Name |
ATP-sensitive inward rectifier potassium channel 1 |
| Target 1 Synonyms |
- ATP-regulated potassium channel ROM-K
- Kir1.1
- 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 |
|
| Target 1 Transmembrane Regions |
|
| Target 1 Essentiality |
Non-Essential |
| Target 1 GenBank ID Protein |
529313  |
| Target 1 UniProtKB/Swiss-Prot ID |
P48048  |
| Target 1 UniProtKB/Swiss-Prot Entry Name |
IRK1_HUMAN  |
| 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  |
| Target 1 GenAtlas ID |
KCNJ1  |
| Target 1 HGNC ID |
HGNC:6255  |
| Target 1 Chromosome Location |
11 |
| Target 1 Locus |
11q24 |
| Target 1 SNPs |
SNPJam Report  |
| Target 1 General References |
- 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
]
- 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
]
- 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
]
- 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
]
|
| Target 1 Drug References |
- 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
]
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed
]
|