DT-Web

DB00414 - Acetohexamide


Identification
Name Acetohexamide
Accession Number DB00414 (APRD00773)
Type small molecule
Description A sulfonylurea hypoglycemic agent that is metabolized in the liver to 1-hydrohexamide. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 324.395
Groups approved
Monoisotopic Weight 324.114377828
Pharmacology
Indication Used in the management of diabetes mellitus type 2 (adult-onset).
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.
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.
Route of elimination 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
Interactions
Drug Interactions
Drug Mechanism of 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
  • Take without regard to meals.
  • Avoid alcohol.

Targets


ATP-sensitive inward rectifier potassium channel 1
Name ATP-sensitive inward rectifier potassium channel 1
Gene Name KCNJ1
Pharmacological action yes
Actions inhibitor
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
DTHybrid score 0.6285

Enzymes


Carbonyl reductase [NADPH] 1
Name Carbonyl reductase [NADPH] 1
Gene Name CBR1
Actions substrate
References
  • -
  • 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
  • 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
  • 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
DTHybrid score 0.6908

Predictions


Id Partner name Gene Name Score
5354 DevB protein VC_A0897 0.138
842 Chloride channel protein 2 CLCN2 0.1214
230 ATP-binding cassette transporter sub-family C member 8 ABCC8 0.1106
781 ATP-sensitive inward rectifier potassium channel 11 KCNJ11 0.039
20 Prostaglandin G/H synthase 1 PTGS1 0.0387
131 Synaptic vesicular amine transporter SLC18A2 0.0377
378 Alpha-2C adrenergic receptor ADRA2C 0.0362
831 D(2) dopamine receptor DRD2 0.0316
4757 Cytochrome P450 2C9 CYP2C9 0.0286
4119 Cytochrome P450 2D6 CYP2D6 0.0262
629 Alpha-2B adrenergic receptor ADRA2B 0.0238
318 Alpha-2A adrenergic receptor ADRA2A 0.0213
6070 Nischarin NISCH 0.0208
3970 Voltage-dependent N-type calcium channel subunit alpha-1B CACNA1B 0.0169
401 Glutamate [NMDA] receptor subunit zeta-1 GRIN1 0.0159
6016 Cytochrome P450 2C19 CYP2C19 0.0138
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0128
1974 Oligopeptide transporter, kidney isoform SLC15A2 0.012
6147 Solute carrier family 22 member 3 SLC22A3 0.012
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.0115
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0111
6144 Solute carrier family 22 member 2 SLC22A2 0.0104
1588 Multidrug resistance protein 1 ABCB1 0.0103
464 Glutamate [NMDA] receptor subunit epsilon-2 GRIN2B 0.0101
6145 Solute carrier family 22 member 1 SLC22A1 0.01
1729 Solute carrier family 22 member 6 SLC22A6 0.0098
3961 G protein-activated inward rectifier potassium channel 4 KCNJ5 0.0095
4512 Cytochrome P450 3A4 CYP3A4 0.0091
6172 ATP-binding cassette sub-family B member 8, mitochondrial ABCB8 0.009
6106 Cytochrome P450 2C18 CYP2C18 0.009
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0087
776 Bile salt export pump ABCB11 0.0083
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0078
638 D(3) dopamine receptor DRD3 0.0076
862 Multidrug resistance-associated protein 1 ABCC1 0.0076
337 NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial NDUFS7 0.0075
214 NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial NDUFS3 0.0075
803 NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial NDUFS2 0.0075
6861 Alcohol dehydrogenase [NADP+] AKR1A1 0.0074
521 ATP-binding cassette transporter sub-family C member 9 ABCC9 0.0074
6168 Solute carrier family 22 member 16 SLC22A16 0.0074
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0071
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.007
132 ATP-binding cassette sub-family A member 1 ABCA1 0.0067
23 D(1A) dopamine receptor DRD1 0.0067
502 5-hydroxytryptamine 2A receptor HTR2A 0.0064
2184 Cystic fibrosis transmembrane conductance regulator CFTR 0.0063
650 Aldo-keto reductase family 1 member C3 AKR1C3 0.0062
4924 Cytochrome P450 2C8 CYP2C8 0.0061
6024 Cytochrome P450 1A1 CYP1A1 0.0059
4120 NADPH--cytochrome P450 reductase POR 0.0056
6107 Cytochrome P450 3A7 CYP3A7 0.0055
2157 NAD(P)H dehydrogenase [quinone] 1 NQO1 0.0055
76 Nitric-oxide synthase, brain NOS1 0.0055
6137 Multidrug resistance-associated protein 6 ABCC6 0.0053
4118 Cytochrome P450 3A5 CYP3A5 0.0052
6148 Multidrug resistance-associated protein 7 ABCC10 0.005
7 Nitric oxide synthase, inducible NOS2 0.0049
4200 Cytochrome P450 1A2 CYP1A2 0.0049
291 Nitric-oxide synthase, endothelial NOS3 0.0048
3947 Xanthine dehydrogenase/oxidase XDH 0.0047
817 DNA topoisomerase 2-alpha TOP2A 0.0046
1898 Cytochrome P450 1B1 CYP1B1 0.0043
6143 Solute carrier family 22 member 7 SLC22A7 0.0039
6030 Cytochrome P450 2B6 CYP2B6 0.0034
587 Serum albumin ALB 0.0031
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