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Identification
Name Tolazamide
Accession Number DB00839 (APRD01267)
Type small molecule
Groups approved
Description

A sulphonylurea hypoglycemic agent with actions and uses similar to those of chlorpropamide. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names
  • Norglycin
  • Tolanase
  • Tolinase
Brand name mixtures Not Available
Categories
  • Hypoglycemic Agents
CAS number 1156-19-0
Weight Average: 311.4
Monoisotopic: 311.130362243
Chemical Formula C14H21N3O3S
InChI Key InChIKey=OUDSBRTVNLOZBN-UHFFFAOYSA-N
InChI
InChI=1S/C14H21N3O3S/c1-12-6-8-13(9-7-12)21(19,20)16-14(18)15-17-10-4-2-3-5-11-17/h6-9H,2-5,10-11H2,1H3,(H2,15,16,18)
Plain Text
IUPAC Name
1-(azepan-1-yl)-3-[(4-methylbenzene)sulfonyl]urea
SMILES
CC1=CC=C(C=C1)S(=O)(=O)NC(=O)NN1CCCCCC1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Sulfonylureas
Substructures
  • Sulfonylureas
  • Sulfonyls
  • Benzene and Derivatives
  • Benzenesulfonamides
  • Heterocyclic compounds
  • Aromatic compounds
  • Sulfonamides
  • Semicarbazides
  • Hydrazine Derivatives
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.
Pharmacodynamics 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.
Absorption Rapidly and well absorbed from the gastrointestinal tract.
Volume of distribution Not Available
Protein binding Not Available
Metabolism

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.
Clearance Not Available
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
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • 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
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Tolazamide 500 mg tablet 1.41 USD tablet
Tolinase 250 mg tablet 1.23 USD tablet
Tolazamide 250 mg tablet 0.79 USD tablet
Tolazamide 100 mg tablet 0.41 USD tablet
Patents Not Available
Properties
State solid
Melting point 170-173 oC
Experimental Properties
Property Value Source
water solubility Solubility at pH 6.0 (mean urinary pH) is 27.8 mg/100 mL PhysProp
logP 2.5 PhysProp
logS -3.68 [ADME Research, USCD] PhysProp
Predicted Properties
Property Value Source
water solubility 3.08e-01 g/l ALOGPS
logP 1.40 ALOGPS
logP 1.91 ChemAxon Molconvert
logS -3.01 ALOGPS
pKa 14.17 ChemAxon Molconvert
hydrogen acceptor count 4 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 78.51 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 81.34 ChemAxon Molconvert
polarizability 32.82 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00379 Link_out
PubChem Compound 5503 Link_out
PubChem Substance 46505642 Link_out
ChemSpider 5302 Link_out
Therapeutic Targets Database DAP000919 Link_out
PharmGKB PA451715 Link_out
Drug Product Database 0 Link_out
RxList http://www.rxlist.com/cgi/generic/tolinase.htm Link_out
Drugs.com http://www.drugs.com/cdi/tolazamide.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Tolazamide Link_out
ATC Codes
  • A10BB05
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. ATP-sensitive inward rectifier potassium channel 1

Pharmacological action: yes
Actions: inhibitor

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

Organism class: human
UniProt ID: P48048 Link_out
Gene: KCNJ1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. 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
  3. 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
  4. 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
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:43

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.