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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
1-(hexahydro-1-Azepinyl)-3-P-tolylsulfonylureaNot AvailableNot Available
1-(hexahydro-1H-Azepin-1-yl)-3-(P-tolylsulfonyl)ureaNot AvailableNot Available
4-(P-Tolylsulfonyl)-1,1-hexamethylenesemicarbazideNot AvailableNot Available
BRN 1323565Not AvailableNot Available
CCRIS 591Not AvailableNot Available
DiabewasNot AvailableNot Available
EINECS 214-588-3Not AvailableNot Available
N-(P-Toluenesulfonyl)-n'-hexamethyleniminoureaNot AvailableNot Available
N-{[(hexahydro-1H-azepin-1-yl)-amino]carbonyl}-4-methylbenzenesulfonamideNot AvailableNot Available
NorglycinNot AvailableNot Available
TolazamidGermanINN
TolazamidaSpanishINN
TolazamideFrenchINN
TolazamidumLatinINN
TolinaseNot AvailableNot Available
U 17835Not AvailableNot Available
U-17835Not AvailableNot Available
Prescription ProductsNot Available
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Tolazamidetablet250 mgoralMylan Pharmaceuticals Inc.2013-01-18Not AvailableUs
Tolazamidetablet500 mgoralMylan Pharmaceuticals Inc.2013-01-18Not AvailableUs
Tolazamidetablet250 mgoralPd Rx Pharmaceuticals, Inc.2010-01-05Not AvailableUs
Tolazamidetablet250 mgoralAmerican Health Packaging2012-02-13Not AvailableUs
Over the Counter ProductsNot Available
International Brands
NameCompany
DesumideHua Shin
EsulinChung Mei
NorglycinPfizer
TolanaseUpjohn
TolinaseNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
CAS number1156-19-0
WeightAverage: 311.4
Monoisotopic: 311.130362243
Chemical FormulaC14H21N3O3S
InChI KeyOUDSBRTVNLOZBN-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-methylbenzenesulfonyl)urea
SMILES
CC1=CC=C(C=C1)S(=O)(=O)NC(=O)NN1CCCCCC1
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzenesulfonamides
Direct ParentBenzenesulfonamides
Alternative Parents
Substituents
  • Tosyl compound
  • Benzenesulfonamide
  • Toluene
  • Sulfonylurea
  • Azepane
  • Aminosulfonyl compound
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • Semicarbazide
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
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
PropertyValueProbability
Human Intestinal Absorption+0.9749
Blood Brain Barrier+0.8467
Caco-2 permeable-0.6444
P-glycoprotein substrateSubstrate0.7039
P-glycoprotein inhibitor INon-inhibitor0.8125
P-glycoprotein inhibitor IINon-inhibitor0.9824
Renal organic cation transporterNon-inhibitor0.8497
CYP450 2C9 substrateSubstrate0.622
CYP450 2D6 substrateNon-substrate0.8816
CYP450 3A4 substrateNon-substrate0.7268
CYP450 1A2 substrateNon-inhibitor0.9274
CYP450 2C9 substrateNon-inhibitor0.9071
CYP450 2D6 substrateNon-inhibitor0.9268
CYP450 2C19 substrateNon-inhibitor0.9104
CYP450 3A4 substrateNon-inhibitor0.84
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.962
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.8461
BiodegradationNot ready biodegradable0.7221
Rat acute toxicity1.8259 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8064
hERG inhibition (predictor II)Non-inhibitor0.8047
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
Tabletoral250 mg
Tabletoral500 mg
Prices
Unit descriptionCostUnit
Tolazamide 500 mg tablet1.41USD tablet
Tolinase 250 mg tablet1.23USD tablet
Tolazamide 250 mg tablet0.79USD tablet
Tolazamide 100 mg tablet0.41USD tablet
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 Solubility0.308 mg/mLALOGPS
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 Area78.51 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity81.34 m3·mol-1ChemAxon
Polarizability32.82 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraMS
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
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

Targets

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

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Drug created on June 13, 2005 07:24 / Updated on October 27, 2013 16:25