Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C15H20N2O4S |
| Molecular Weight | 324.395 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(=O)C1=CC=C(C=C1)S(=O)(=O)NC(=O)NC2CCCCC2
InChI
InChIKey=VGZSUPCWNCWDAN-UHFFFAOYSA-N
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)
| Molecular Formula | C15H20N2O4S |
| Molecular Weight | 324.395 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionCurator's Comment: description was created based on several sources, including
http://www.druglib.com/activeingredient/acetohexamide/
Curator's Comment: description was created based on several sources, including
http://www.druglib.com/activeingredient/acetohexamide/
Acetohexamide (trade name Dymelor) is a first-generation sulfonylurea medication used to treat diabetes mellitus type 2, particularly in people whose diabetes cannot be controlled by diet alone. 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 binds to an ATP-dependent K+ channel on the cell membrane of pancreatic beta cells. This inhibits a tonic, hyperpolarizing out flux 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 granule with the cell membrane, and therefore increased secretion of (pro) insulin. Acetohexamide 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. Symptoms of an acetohexamide overdose include hunger, nausea, anxiety, cold sweats, weakness, drowsiness, unconsciousness, and coma. Acetohexamide has been discontinued in the US market.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2096972 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=22260657 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Palliative | DYMELOR Approved UseUnknown Launch Date1964 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
60 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12458186/ |
10 mg/kg single, intravenous dose: 10 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
HYDROXYHEXAMIDE plasma | Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FASTED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
289 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12458186/ |
10 mg/kg single, intravenous dose: 10 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
HYDROXYHEXAMIDE plasma | Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
4.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12458186/ |
10 mg/kg single, intravenous dose: 10 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
HYDROXYHEXAMIDE plasma | Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FASTED |
Doses
| Dose | Population | Adverse events |
|---|---|---|
2 g 1 times / day multiple, oral Highest studied dose Dose: 2 g, 1 times / day Route: oral Route: multiple Dose: 2 g, 1 times / day Sources: |
unhealthy, 61.6 (26-87) Health Status: unhealthy Age Group: 61.6 (26-87) Sex: M+F Sources: |
Disc. AE: Diffuse pain, Diarrhea... AEs leading to discontinuation/dose reduction: Diffuse pain Sources: Diarrhea |
0.5 g 1 times / day multiple, oral Recommended Dose: 0.5 g, 1 times / day Route: oral Route: multiple Dose: 0.5 g, 1 times / day Sources: |
unhealthy, 74 |
Other AEs: Hypoglycemia... |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Diarrhea | Disc. AE | 2 g 1 times / day multiple, oral Highest studied dose Dose: 2 g, 1 times / day Route: oral Route: multiple Dose: 2 g, 1 times / day Sources: |
unhealthy, 61.6 (26-87) Health Status: unhealthy Age Group: 61.6 (26-87) Sex: M+F Sources: |
| Diffuse pain | Disc. AE | 2 g 1 times / day multiple, oral Highest studied dose Dose: 2 g, 1 times / day Route: oral Route: multiple Dose: 2 g, 1 times / day Sources: |
unhealthy, 61.6 (26-87) Health Status: unhealthy Age Group: 61.6 (26-87) Sex: M+F Sources: |
| Hypoglycemia | 0.5 g 1 times / day multiple, oral Recommended Dose: 0.5 g, 1 times / day Route: oral Route: multiple Dose: 0.5 g, 1 times / day Sources: |
unhealthy, 74 |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no [Activation >10 uM] | ||||
| no [Activation >10 uM] | ||||
| no [Activation >10 uM] | ||||
| no [Activation >10 uM] | ||||
| no [Activation >10 uM] |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
Sources: https://go.drugbank.com/drugs/DB00414 |
yes |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Molecular and biochemical characterisation of human short-chain dehydrogenase/reductase member 3 (DHRS3). | 2015-06-05 |
|
| Epac2: a sulfonylurea receptor? | 2012-02 |
|
| Detection of heterogeneous drug-protein binding by frontal analysis and high-performance affinity chromatography. | 2011-12-09 |
|
| Use of peak decay analysis and affinity microcolumns containing silica monoliths for rapid determination of drug-protein dissociation rates. | 2011-04-15 |
|
| Chromatographic studies of changes in binding of sulfonylurea drugs to human serum albumin due to glycation and fatty acids. | 2010-11-15 |
|
| Chromatographic analysis of acetohexamide binding to glycated human serum albumin. | 2010-10-15 |
|
| Characterization of the binding of sulfonylurea drugs to HSA by high-performance affinity chromatography. | 2010-06-01 |
|
| A new method of urethroplasty for prevention of fistula in female-to-male gender reassignment surgery. | 2010-06 |
|
| Adverse drug effects in hospitalized elderly: data from the healthcare cost and utilization project. | 2010 |
|
| Pancreatic beta-cell signaling: toward better understanding of diabetes and its treatment. | 2010 |
|
| Rosiglitazone and myocardial infarction in patients previously prescribed metformin. | 2009-06-27 |
|
| Metformin, sulfonylureas, or other antidiabetes drugs and the risk of lactic acidosis or hypoglycemia: a nested case-control analysis. | 2008-11 |
|
| Differential pharmacokinetics of acetohexamide in male Wistar-Imamichi and Sprague-Dawley rats: role of microsomal carbonyl reductase. | 2005-01 |
|
| [Studies for analyzing the prohibited ingredients such as acetohexamide in cosmetics]. | 2005 |
|
| Strain- and sex-related differences of carbonyl reductase activities in kidney microsomes and cytosol of rats. | 2004-11-24 |
|
| Analysis of synthetic anti-diabetic drugs in adulterated traditional Chinese medicines by high-performance capillary electrophoresis. | 2003-09-19 |
|
| Selection of drugs to test the specificity of the Tg.AC assay by screening for induction of the gadd153 promoter in vitro. | 2003-08 |
|
| Barriers to self-monitoring of blood glucose among adults with diabetes in an HMO: a cross sectional study. | 2003-03-19 |
|
| [A 50-year history of new drugs in Japan-the development and progress of anti-diabetic drugs and the epidemiological aspects of diabetes mellitus]. | 2003 |
|
| Sex-dependent pharmacokinetics of S(-)-hydroxyhexamide, a pharmacologically active metabolite of acetohexamide, in rats. | 2002-12 |
|
| Cadmium exposure decreases androgen-dependent metabolism of acetohexamide in liver microsomes of male rats through its testicular toxicity. | 2002-02 |
|
| Hormonal regulation of male-specific 20beta-hydroxysteroid dehydrogenase with carbonyl reductase-like activity present in kidney microsomes of rats. | 2001-10 |
|
| Hypoglycemic effect of S(-)-hydroxyhexamide, a major metabolite of acetohexamide, and its enantiomer R(+)-hydroxyhexamide. | 2001-09-07 |
|
| [Strain-, sex- and species-related differences of acetohexamide reductase and 20 beta-hydroxysteroid dehydrogenase activities in liver microsomes of experimental animals]. | 2001-01 |
|
| The structure and function of the ATP-sensitive K+ channel in insulin-secreting pancreatic beta-cells. | 1999-04 |
|
| Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor. | 1995-11-17 |
|
| Reversible cholestatic hepatitis caused by acetohexamide. | 1989-06 |
|
| Reduction of the severity of nephropathy in aging Fischer 344 rats treated with analogs of arylsulfonyluria. | 1979-07 |
|
| Prolonged coma after acetohexamide ingestion. | 1967-07-10 |
|
| Hypoglycemic stupor caused by acetohexamide. | 1966-06-02 |
| Substance Class |
Chemical
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| Record UNII |
QGC8W08I6I
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Validated (UNII)
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LIVERTOX |
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A10BB31
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173
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6793
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CHEMBL1589
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SUB05223MIG
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DTXSID7020007
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ACETOHEXAMIDE
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m1331
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Acetohexamide
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1134
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DB00414
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759128
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100000087938
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D000092
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C47380
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968-81-0
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213-530-4
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28052
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BINDER->LIGAND |
| Related Record | Type | Details | ||
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METABOLITE ACTIVE -> PARENT |
Metabolite to parent drug I non-uraemic human plasma 1.0-2.2
METABOLITE TO PARENT DRUG RATIO
PLASMA
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METABOLITE ACTIVE -> PARENT |
URINE
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ACTIVE MOIETY |
| Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
|---|---|---|---|---|---|---|
| Biological Half-life | PHARMACOKINETIC |
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