DT-Web

DB00839 - Tolazamide


Identification
Name Tolazamide
Accession Number DB00839 (APRD01267)
Type small molecule
Description A sulphonylurea hypoglycemic agent with actions and uses similar to those of chlorpropamide. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 311.4
Groups approved
Monoisotopic Weight 311.130362243
Pharmacology
Indication For use as an adjunct to diet to lower the blood glucose in patients with non-insulin dependent diabetes mellitus (Type II) whose hyperglycemia cannot be satisfactorily controlled by diet alone.
Mechanism of action Sulfonylureas likely bind to ATP-sensitive potassium-channel receptors on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Depolarization stimulates calcium ion influx through voltage-sensitive calcium channels, raising intracellular concentrations of calcium ions, which induces the secretion, or exocytosis, of insulin.
Absorption Rapidly and well absorbed from the gastrointestinal tract.
Protein binding Not Available
Biotransformation Tolazamide is metabolized to five major metabolites ranging in hypoglycemic activity from 0 to 70%.
Route of elimination Tolazamide is metabolized to five major metabolites ranging in hypoglycemic activity from 0% to 70%. They are excreted principally in the urine.
Toxicity Overdosage of sulfonylureas can produce hypoglycemia. Severe hypoglycemic reactions with coma, seizure, or other neurological impairment occur infrequently, but constitute medical emergencies requiring immediate hospitalization.
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 the sulfonylurea, tolazamide.
Amifostine Additive hypotensive effects may occur. At chemotherapeutic doses of Amifostine, Tolazamide should be withheld for 24 hours prior to Amifostine administration. Use caution at lower doses of Amifostine.
Atenolol The beta-blocker, atenolol, may decrease symptoms of hypoglycemia.
Bisoprolol The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.
Carvedilol The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
Chloramphenicol Chloramphenicol may increase the effect of sulfonylurea, tolazamide.
Clofibrate Clofibrate may increase the effect of sulfonylurea, tolazamide.
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 increases the effect of the hypoglycemic agent
Pindolol The beta-blocker, pindolol, may decrease symptoms of hypoglycemia.
Propranolol The beta-blocker, propranolol, may decrease symptoms of hypoglycemia.
Rifampin Rifampin may decrease the effect of sulfonylurea, tolazamide.
Rituximab Additive hypotensive effects may occur. Consider withholding Tolazamide for 12 hours prior to administration of Rituximab.
Somatropin recombinant Somatropin may antagonize the hypoglycemic effect of Tolazamide. Dose adjustments of Tolazamide may be required.
Timolol The beta-blocker, timolol, may decrease symptoms of hypoglycemia.
Food Interactions Not Available

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
  • Szabo C, Salzman AL: Inhibition of ATP-activated potassium channels exerts pressor effects and improves survival in a rat model of severe hemorrhagic shock. Shock. 1996 Jun;5(6):391-4. - Pubmed
  • Asano K, Cortes P, Garvin JL, Riser BL, Rodriguez-Barbero A, Szamosfalvi B, Yee J: Characterization of the rat mesangial cell type 2 sulfonylurea receptor. Kidney Int. 1999 Jun;55(6):2289-98. - Pubmed
DTHybrid score 0.5516

Predictions


Id Partner name Gene Name Score
230 ATP-binding cassette transporter sub-family C member 8 ABCC8 0.1106
5251 Carbonyl reductase [NADPH] 1 CBR1 0.0661
781 ATP-sensitive inward rectifier potassium channel 11 KCNJ11 0.039
20 Prostaglandin G/H synthase 1 PTGS1 0.0387
378 Alpha-2C adrenergic receptor ADRA2C 0.0362
4757 Cytochrome P450 2C9 CYP2C9 0.0239
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
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
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
6106 Cytochrome P450 2C18 CYP2C18 0.009
6016 Cytochrome P450 2C19 CYP2C19 0.0088
521 ATP-binding cassette transporter sub-family C member 9 ABCC9 0.0074
132 ATP-binding cassette sub-family A member 1 ABCA1 0.0067
2184 Cystic fibrosis transmembrane conductance regulator CFTR 0.0063
4924 Cytochrome P450 2C8 CYP2C8 0.0061
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0042
776 Bile salt export pump ABCB11 0.004
6143 Solute carrier family 22 member 7 SLC22A7 0.0039
862 Multidrug resistance-associated protein 1 ABCC1 0.0037
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0034
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0034
587 Serum albumin ALB 0.0031
1588 Multidrug resistance protein 1 ABCB1 0.0026
4512 Cytochrome P450 3A4 CYP3A4 0.0023
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