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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
1-(hexahydro-1-Azepinyl)-3-P-tolylsulfonylurea
1-(hexahydro-1H-Azepin-1-yl)-3-(P-tolylsulfonyl)urea
4-(P-Tolylsulfonyl)-1,1-hexamethylenesemicarbazide
BRN 1323565
CCRIS 591
Diabewas
EINECS 214-588-3
N-(P-Toluenesulfonyl)-n'-hexamethyleniminourea
N-{[(hexahydro-1H-azepin-1-yl)-amino]carbonyl}-4-methylbenzenesulfonamide
Norglycin
Tolazamid
Tolazamida
Tolazamide
Tolazamidum
Tolinase
U 17835
U-17835
External Identifiers
  • U 17835
Prescription ProductsNot Available
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Tolazamidetablet250 mg/1oralMylan Pharmaceuticals Inc.2013-01-18Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tolazamidetablet250 mg/1oralPd Rx Pharmaceuticals, Inc.2010-01-05Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tolazamidetablet500 mg/1oralMylan Pharmaceuticals Inc.2013-01-18Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
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 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-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 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9268
CYP450 2C19 inhibitorNon-inhibitor0.9104
CYP450 3A4 inhibitorNon-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
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
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/1
Tabletoral500 mg/1
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
Spectra
Spectrum TypeDescriptionSplash Key
MSMass Spectrum (Electron Ionization)splash10-zk00000000-41e71d724a7515763bb7View in MoNA
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesA10BB05
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcetohexamideAcetohexamide may increase the hypoglycemic activities of Tolazamide.
Acetylsalicylic acidAcetylsalicylic acid may increase the hypoglycemic activities of Tolazamide.
AlogliptinAlogliptin may increase the hypoglycemic activities of Tolazamide.
AmitriptylineAmitriptyline may increase the hypoglycemic activities of Tolazamide.
CanagliflozinCanagliflozin may increase the hypoglycemic activities of Tolazamide.
CarbocisteineThe risk or severity of adverse effects can be increased when Tolazamide is combined with Carbocisteine.
ChloramphenicolThe metabolism of Tolazamide can be decreased when combined with Chloramphenicol.
ChlorpropamideChlorpropamide may increase the hypoglycemic activities of Tolazamide.
CimetidineThe serum concentration of Tolazamide can be increased when it is combined with Cimetidine.
DexketoprofenThe risk or severity of adverse effects can be increased when Dexketoprofen is combined with Tolazamide.
DicoumarolTolazamide may increase the anticoagulant activities of Dicoumarol.
DihydrotestosteroneDihydrotestosterone may increase the hypoglycemic activities of Tolazamide.
EthanolThe risk or severity of adverse effects can be increased when Tolazamide is combined with Ethanol.
ExenatideExenatide may increase the hypoglycemic activities of Tolazamide.
FenofibrateFenofibrate may increase the hypoglycemic activities of Tolazamide.
FluconazoleThe serum concentration of Tolazamide can be increased when it is combined with Fluconazole.
GliclazideGliclazide may increase the hypoglycemic activities of Tolazamide.
GlimepirideGlimepiride may increase the hypoglycemic activities of Tolazamide.
GliquidoneGliquidone may increase the hypoglycemic activities of Tolazamide.
GlyburideGlyburide may increase the hypoglycemic activities of Tolazamide.
Insulin AspartInsulin Aspart may increase the hypoglycemic activities of Tolazamide.
Insulin DetemirInsulin Detemir may increase the hypoglycemic activities of Tolazamide.
Insulin GlargineInsulin Glargine may increase the hypoglycemic activities of Tolazamide.
Insulin GlulisineInsulin Glulisine may increase the hypoglycemic activities of Tolazamide.
Insulin LisproInsulin Lispro may increase the hypoglycemic activities of Tolazamide.
Insulin RegularInsulin Regular may increase the hypoglycemic activities of Tolazamide.
Insulin, isophaneInsulin, isophane may increase the hypoglycemic activities of Tolazamide.
LeuprolideThe therapeutic efficacy of Tolazamide can be decreased when used in combination with Leuprolide.
LinagliptinLinagliptin may increase the hypoglycemic activities of Tolazamide.
Lipoic AcidLipoic Acid may increase the hypoglycemic activities of Tolazamide.
MecamylamineThe risk or severity of adverse effects can be increased when Tolazamide is combined with Mecamylamine.
MetforminMetformin may increase the hypoglycemic activities of Tolazamide.
MetreleptinMetreleptin may increase the hypoglycemic activities of Tolazamide.
MiconazoleMiconazole may increase the hypoglycemic activities of Tolazamide.
NadololNadolol may increase the hypoglycemic activities of Tolazamide.
OxandroloneOxandrolone may increase the hypoglycemic activities of Tolazamide.
ParoxetineParoxetine may increase the hypoglycemic activities of Tolazamide.
PegvisomantPegvisomant may increase the hypoglycemic activities of Tolazamide.
PhenelzinePhenelzine may increase the hypoglycemic activities of Tolazamide.
PorfimerTolazamide may increase the photosensitizing activities of Porfimer.
ProbenecidThe protein binding of Tolazamide can be decreased when combined with Probenecid.
RanitidineThe serum concentration of Tolazamide can be increased when it is combined with Ranitidine.
RepaglinideRepaglinide may increase the hypoglycemic activities of Tolazamide.
RifampicinThe serum concentration of Tolazamide can be decreased when it is combined with Rifampicin.
Salicylate-sodiumSalicylate-sodium may increase the hypoglycemic activities of Tolazamide.
SaxagliptinSaxagliptin may increase the hypoglycemic activities of Tolazamide.
SitagliptinSitagliptin may increase the hypoglycemic activities of Tolazamide.
SparfloxacinSparfloxacin may increase the hypoglycemic activities of Tolazamide.
SulfisoxazoleSulfisoxazole may increase the hypoglycemic activities of Tolazamide.
TestosteroneTestosterone may increase the hypoglycemic activities of Tolazamide.
TolbutamideTolbutamide may increase the hypoglycemic activities of Tolazamide.
TranylcypromineTranylcypromine may increase the hypoglycemic activities of Tolazamide.
TrichlormethiazideThe therapeutic efficacy of Tolazamide can be decreased when used in combination with Trichlormethiazide.
TroglitazoneTroglitazone may increase the hypoglycemic activities of Tolazamide.
VerteporfinTolazamide may increase the photosensitizing activities of Verteporfin.
VildagliptinVildagliptin may increase the hypoglycemic activities of Tolazamide.
VoriconazoleThe serum concentration of Tolazamide can be increased when it is combined with Voriconazole.
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