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Identification
NameTolazamide
Accession NumberDB00839  (APRD01267)
Typesmall molecule
Groupsapproved
Description

A sulphonylurea hypoglycemic agent with actions and uses similar to those of chlorpropamide. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
TolazamidGermanINN
TolazamidaSpanishINN
TolazamideFrenchINN
TolazamidumLatinINN
SaltsNot Available
Brand names
NameCompany
DesumideHua Shin
EsulinChung Mei
NorglycinPfizer
TolanaseUpjohn
TolazamideSandoz
TolinaseNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number1156-19-0
WeightAverage: 311.4
Monoisotopic: 311.130362243
Chemical FormulaC14H21N3O3S
InChI KeyInChIKey=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)
IUPAC Name
1-(azepan-1-yl)-3-[(4-methylbenzene)sulfonyl]urea
SMILES
CC1=CC=C(C=C1)S(=O)(=O)NC(=O)NN1CCCCCC1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassBenzenesulfonamides
Direct parentBenzenesulfonamides
Alternative parentsToluenes; Sulfonylureas; Azepanes; Sulfonyls; Sulfonamides; Semicarbazides; Polyamines
Substituentsazepane; sulfonylurea; toluene; sulfonic acid derivative; sulfonyl; sulfonamide; semicarbazide; polyamine; amine; hydrazine derivative; organonitrogen compound
Classification descriptionThis compound belongs to the benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring.
Pharmacology
IndicationFor 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.
PharmacodynamicsTolazamide 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 actionSulfonylureas 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.
AbsorptionRapidly and well absorbed from the gastrointestinal tract.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Tolazamide is metabolized to five major metabolites ranging in hypoglycemic activity from 0 to 70%.

Route of eliminationTolazamide is metabolized to five major metabolites ranging in hypoglycemic activity from 0% to 70%. They are excreted principally in the urine.
Half lifeThe average biological half-life of the drug is 7 hours.
ClearanceNot Available
ToxicityOverdosage 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Non-inhibitor 0.9268
CYP450 2C19 substrate Non-inhibitor 0.9104
CYP450 3A4 substrate 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
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
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Tolazamide 500 mg tablet1.41USDtablet
Tolinase 250 mg tablet1.23USDtablet
Tolazamide 250 mg tablet0.79USDtablet
Tolazamide 100 mg tablet0.41USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point170-173 °CPhysProp
water solubility65.4 mg/L (at 30 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP2.69SANGSTER (1993)
logS-3.68ADME Research, USCD
Predicted Properties
PropertyValueSource
water solubility3.08e-01 g/lALOGPS
logP1.4ALOGPS
logP1.91ChemAxon
logS-3ALOGPS
pKa (strongest acidic)4.07ChemAxon
pKa (strongest basic)1.61ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count2ChemAxon
polar surface area78.51ChemAxon
rotatable bond count2ChemAxon
refractivity81.34ChemAxon
polarizability32.82ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00379
PubChem Compound5503
PubChem Substance46505642
ChemSpider5302
Therapeutic Targets DatabaseDAP000919
PharmGKBPA164774902
RxListhttp://www.rxlist.com/cgi/generic/tolinase.htm
Drugs.comhttp://www.drugs.com/cdi/tolazamide.html
WikipediaTolazamide
ATC CodesA10BB05
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcebutololAcebutolol may decrease symptoms of hypoglycemia and increase the time required for the body to compensate for hypoglycemia.
Acetylsalicylic acidAcetylsalicylic acid increases the effect of the sulfonylurea, tolazamide.
AmifostineAdditive 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.
AtenololThe beta-blocker, atenolol, may decrease symptoms of hypoglycemia.
BisoprololThe beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.
CarvedilolThe beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
ChloramphenicolChloramphenicol may increase the effect of sulfonylurea, tolazamide.
ClofibrateClofibrate may increase the effect of sulfonylurea, tolazamide.
EsmololThe beta-blocker, esmolol, may decrease symptoms of hypoglycemia.
LabetalolThe beta-blocker, labetalol, may decrease symptoms of hypoglycemia.
MetoprololThe beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.
NadololThe beta-blocker, nadolol, may decrease symptoms of hypoglycemia.
OxprenololThe beta-blocker, oxprenolol, may decrease symptoms of hypoglycemia.
PhenylbutazonePhenylbutazone increases the effect of the hypoglycemic agent
PindololThe beta-blocker, pindolol, may decrease symptoms of hypoglycemia.
PropranololThe beta-blocker, propranolol, may decrease symptoms of hypoglycemia.
RifampicinRifampin may decrease the effect of sulfonylurea, tolazamide.
RituximabAdditive hypotensive effects may occur. Consider withholding Tolazamide for 12 hours prior to administration of Rituximab.
Somatropin recombinantSomatropin may antagonize the hypoglycemic effect of Tolazamide. Dose adjustments of Tolazamide may be required.
TimololThe beta-blocker, timolol, may decrease symptoms of hypoglycemia.
Food InteractionsNot Available

1. ATP-sensitive inward rectifier potassium channel 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
ATP-sensitive inward rectifier potassium channel 1 P48048 Details

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 October 27, 2013 16:25