- Accession Number
- DB00839 (APRD01267)
- Small Molecule
- Approved, Investigational
A sulphonylurea hypoglycemic agent with actions and uses similar to those of chlorpropamide.
- External IDs
- AI3-50826 / BRN 1323565 / CCRIS 591 / EINECS 214-588-3 / HSDB 3192 / NCI-C03327 / NSC-70762 / U 17835 / U-17835
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Tolinase Tablet 500 mg/1 Oral UNSPECIFIED 2006-04-11 Not applicable Tolinase Tablet 100 mg/1 Oral UNSPECIFIED 2006-04-11 Not applicable Tolinase Tablet 250 mg/1 Oral UNSPECIFIED 2006-04-11 Not applicable
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Tolazamide Tablet 250 mg/1 Oral PD-Rx Pharmaceuticals, Inc. 2010-01-05 Not applicable Tolazamide Tablet 250 mg/1 Oral Physicians Total Care, Inc. 1995-02-02 2012-06-30 Tolazamide Tablet 500 mg/1 Oral Mylan Pharmaceuticals Inc. 2013-01-18 Not applicable Tolazamide Tablet 250 mg/1 Oral Mylan Pharmaceuticals Inc. 2013-01-18 Not applicable Tolazamide Tablet 250 mg/1 Oral Amerincan Health Packaging 2012-02-13 2015-05-31
- International/Other Brands
- Desumide (Hua Shin) / Diabewas / Esulin (Chung Mei) / Norglycin (Pfizer) / Tolanase (Upjohn) / Tolinase
- CAS number
- Average: 311.4
- Chemical Formula
- InChI Key
- IUPAC Name
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.
- Associated Conditions
Tolazamide is an oral blood glucose lowering drug of the sulfonylurea class. Tolazamide appears to lower the blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. The mechanism by which tolazamide lowers blood glucose during long-term administration has not been clearly established. With chronic administration in Type II diabetic patients, the blood glucose lowering effect persists despite a gradual decline in the insulin secretory response to the drug. Extrapancreatic effects may be involved in the mechanism of action of oral sulfonylurea hypoglycemic drugs. Some patients who are initially responsive to oral hypoglycemic drugs, including tolazamide, may become unresponsive or poorly responsive over time. Alternatively, tolazamide may be effective in some patients who have become unresponsive to one or more other sulfonylurea drugs. In addition to its blood glucose lowering actions, tolazamide produces a mild diuresis by enhancement of renal free water clearance.
- 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.
Target Actions Organism ASulfonylurea receptor 1, Kir6.2blocker Humans
Rapidly and well absorbed from the gastrointestinal tract.
- Volume of distribution
- Not Available
- Protein binding
- Not Available
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.
- Half life
The average biological half-life of the drug is 7 hours.
- Not Available
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
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
- Drug Interactions
Drug Interaction (R)-warfarin Tolazamide may increase the anticoagulant activities of (R)-warfarin. (S)-Warfarin Tolazamide may increase the anticoagulant activities of (S)-Warfarin. 2,4-thiazolidinedione The risk or severity of hypoglycemia can be increased when Tolazamide is combined with 2,4-thiazolidinedione. 4-hydroxycoumarin Tolazamide may increase the anticoagulant activities of 4-hydroxycoumarin. 5-(2-methylpiperazine-1-sulfonyl)isoquinoline The therapeutic efficacy of Tolazamide can be increased when used in combination with 5-(2-methylpiperazine-1-sulfonyl)isoquinoline. Abacavir Tolazamide may decrease the excretion rate of Abacavir which could result in a higher serum level. Abatacept The metabolism of Tolazamide can be increased when combined with Abatacept. Abiraterone The metabolism of Tolazamide can be decreased when combined with Abiraterone. Acarbose The risk or severity of hypoglycemia can be increased when Acarbose is combined with Tolazamide. Acebutolol Acebutolol may increase the hypoglycemic activities of Tolazamide.
- Food Interactions
- Not Available
- General References
- Tal A: Oral hypoglycemic agents in the treatment of type II diabetes. Am Fam Physician. 1993 Nov 1;48(6):1089-95. [PubMed:8237731]
- Granberry MC, Fonseca VA: Cardiovascular risk factors associated with insulin resistance: effects of oral antidiabetic agents. Am J Cardiovasc Drugs. 2005;5(3):201-9. [PubMed:15901207]
- External Links
- ATC Codes
- A10BB05 — Tolazamide
- Clinical Trials
Phase Status Purpose Conditions Count 2 Completed Treatment Impaired Glucose Tolerance (IGT) / Type 2 Diabetes Mellitus 1 Not Available Completed Not Available Type 2 Diabetes Mellitus 3
- Barr laboratories inc
- Duramed pharmaceuticals inc sub barr laboratories inc
- Interpharm inc
- Ivax pharmaceuticals inc sub teva pharmaceuticals usa
- Mutual pharmaceutical co inc
- Mylan pharmaceuticals inc
- Par pharmaceutical inc
- Sandoz inc
- Superpharm corp
- Usl pharma inc
- Watson laboratories inc
- Pharmacia and upjohn co
- Apotheca Inc.
- Central Texas Community Health Centers
- Dispensing Solutions
- Ivax Pharmaceuticals
- Kaiser Foundation Hospital
- Major Pharmaceuticals
- Murfreesboro Pharmaceutical Nursing Supply
- Mutual Pharmaceutical Co.
- PCA LLC
- PD-Rx Pharmaceuticals Inc.
- Pharmaceutical Utilization Management Program VA Inc.
- Physicians Total Care Inc.
- Dosage forms
Form Route Strength Tablet Oral 100 mg/1 Tablet Oral 250 mg/1 Tablet Oral 500 mg/1
Unit description Cost Unit Tolazamide 500 mg tablet 1.41USD tablet Tolinase 250 mg tablet 1.23USD tablet Tolazamide 250 mg tablet 0.79USD tablet Tolazamide 100 mg tablet 0.41USD tabletDrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
- Not Available
- Experimental Properties
Property Value Source melting point (°C) 170-173 °C PhysProp water solubility 65.4 mg/L (at 30 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992) logP 2.69 SANGSTER (1993) logS -3.68 ADME Research, USCD
- Predicted Properties
Property Value Source Water Solubility 0.308 mg/mL ALOGPS logP 1.4 ALOGPS logP 1.91 ChemAxon logS -3 ALOGPS pKa (Strongest Acidic) 4.07 ChemAxon pKa (Strongest Basic) 1.61 ChemAxon Physiological Charge -1 ChemAxon Hydrogen Acceptor Count 4 ChemAxon Hydrogen Donor Count 2 ChemAxon Polar Surface Area 78.51 Å2 ChemAxon Rotatable Bond Count 2 ChemAxon Refractivity 81.34 m3·mol-1 ChemAxon Polarizability 32.82 Å3 ChemAxon Number of Rings 2 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon
- Predicted ADMET features
Property Value Probability Human Intestinal Absorption + 0.9749 Blood Brain Barrier + 0.8467 Caco-2 permeable - 0.6444 P-glycoprotein substrate Substrate 0.7039 P-glycoprotein inhibitor I Non-inhibitor 0.8125 P-glycoprotein inhibitor II Non-inhibitor 0.9824 Renal organic cation transporter Non-inhibitor 0.8497 CYP450 2C9 substrate Substrate 0.622 CYP450 2D6 substrate Non-substrate 0.8816 CYP450 3A4 substrate Non-substrate 0.7268 CYP450 1A2 substrate Non-inhibitor 0.9274 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.9268 CYP450 2C19 inhibitor Non-inhibitor 0.9104 CYP450 3A4 inhibitor Non-inhibitor 0.84 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.962 Ames test Non AMES toxic 0.9133 Carcinogenicity Non-carcinogens 0.8461 Biodegradation Not ready biodegradable 0.7221 Rat acute toxicity 1.8259 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8064 hERG inhibition (predictor II) Non-inhibitor 0.8047
- Mass Spec (NIST)
- Not Available
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Mass Spectrum (Electron Ionization) MS splash10-06r6-9500000000-41e71d724a7515763bb7 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available LC-MS/MS Spectrum - LC-ESI-qTof , Positive LC-MS/MS Not Available LC-MS/MS Spectrum - LC-ESI-qTof , Positive LC-MS/MS Not Available MS/MS Spectrum - , positive LC-MS/MS splash10-001i-0119000000-08f98037ec7196f2922f MS/MS Spectrum - , positive LC-MS/MS splash10-00kg-6901000000-edb181b207ba0c040d5e
- This compound belongs to the class of organic compounds known as benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring.
- Organic compounds
- Super Class
- Benzene and substituted derivatives
- Sub Class
- Direct Parent
- Alternative Parents
- Tosyl compounds / Benzenesulfonyl compounds / Sulfonylureas / Azepanes / Organosulfonic acids and derivatives / Aminosulfonyl compounds / Hydrazones / Azacyclic compounds / Organopnictogen compounds / Organooxygen compoundsOrganic oxides / Hydrocarbon derivatives show 2 more
- Benzenesulfonamide / Tosyl compound / Benzenesulfonyl group / Azepane / Toluene / Sulfonylurea / Organic sulfonic acid or derivatives / Organosulfonic acid or derivatives / Aminosulfonyl compound / SulfonylHydrazone / Azacycle / Organoheterocyclic compound / Organic nitrogen compound / Hydrocarbon derivative / Organic oxide / Organosulfur compound / Organooxygen compound / Organonitrogen compound / Organopnictogen compound / Organic oxygen compound / Aromatic heteromonocyclic compound show 12 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- N-sulfonylurea (CHEBI:9613)
- 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:8799949]
- 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:10354277]
- Pharmacological action
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- Uniprot ID
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
- May M, Schindler C: Clinically and pharmacologically relevant interactions of antidiabetic drugs. Ther Adv Endocrinol Metab. 2016 Apr;7(2):69-83. doi: 10.1177/2042018816638050. Epub 2016 Mar 31. [PubMed:27092232]
Drug created on June 13, 2005 07:24 / Updated on December 16, 2018 06:43