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Details

Stereochemistry ACHIRAL
Molecular Formula C14H21N3O3S
Molecular Weight 311.4015
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TOLAZAMIDE

SMILES

Cc1ccc(cc1)S(=O)(=O)NC(=NN2CCCCCC2)O

InChI

InChIKey=OUDSBRTVNLOZBN-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Molecular Formula C14H21N3O3S
Molecular Weight 311.4015
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: Description was created based on several sources, including https://www.drugs.com/pro/tolinase.html

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. 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. Tolazamide is used 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.

Originator

Curator's Comment:: was developed and marketed as Tolinase® by Pharmacia and Upjohn

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
5.861 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Tolazamide

Approved Use

Indicated as an adjunct to diet to lower the blood glucose in patients with noninsulin dependent diabetes mellitus (Type II) whose hyperglycemia cannot be satisfactorily controlled by diet alone.

Launch Date

4.65523212E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
21.8 μg/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TOLAZAMIDE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
260 μg × h/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TOLAZAMIDE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
4.6 h
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TOLAZAMIDE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
0.5 g 2 times / day multiple, oral
Recommended
Dose: 0.5 g, 2 times / day
Route: oral
Route: multiple
Dose: 0.5 g, 2 times / day
Sources:
unhealthy, 50
n = 8
Health Status: unhealthy
Condition: diabetes mellitus
Age Group: 50
Sex: M+F
Population Size: 8
Sources:
0.75 g 1 times / day single, oral
Overdose
Dose: 0.75 g, 1 times / day
Route: oral
Route: single
Dose: 0.75 g, 1 times / day
Sources:
unhealthy, 59
n = 1
Health Status: unhealthy
Condition: diabetes mellitus
Age Group: 59
Sex: F
Population Size: 1
Sources:
Other AEs: Shakiness...
1 g 1 times / day single, oral
Overdose
Dose: 1 g, 1 times / day
Route: oral
Route: single
Dose: 1 g, 1 times / day
Sources:
unhealthy, 62
n = 1
Health Status: unhealthy
Condition: diabetes mellitus
Age Group: 62
Sex: F
Population Size: 1
Sources:
Other AEs: Dizziness...
0.5 g 1 times / day single, oral
Overdose
Dose: 0.5 g, 1 times / day
Route: oral
Route: single
Dose: 0.5 g, 1 times / day
Sources:
unhealthy, 69
n = 1
Health Status: unhealthy
Condition: diabetes mellitus
Age Group: 69
Sex: F
Population Size: 1
Sources:
Other AEs: Dizziness...
AEs

AEs

AESignificanceDosePopulation
Shakiness
0.75 g 1 times / day single, oral
Overdose
Dose: 0.75 g, 1 times / day
Route: oral
Route: single
Dose: 0.75 g, 1 times / day
Sources:
unhealthy, 59
n = 1
Health Status: unhealthy
Condition: diabetes mellitus
Age Group: 59
Sex: F
Population Size: 1
Sources:
Dizziness
1 g 1 times / day single, oral
Overdose
Dose: 1 g, 1 times / day
Route: oral
Route: single
Dose: 1 g, 1 times / day
Sources:
unhealthy, 62
n = 1
Health Status: unhealthy
Condition: diabetes mellitus
Age Group: 62
Sex: F
Population Size: 1
Sources:
Dizziness
0.5 g 1 times / day single, oral
Overdose
Dose: 0.5 g, 1 times / day
Route: oral
Route: single
Dose: 0.5 g, 1 times / day
Sources:
unhealthy, 69
n = 1
Health Status: unhealthy
Condition: diabetes mellitus
Age Group: 69
Sex: F
Population Size: 1
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes
Drug as victim
PubMed

PubMed

TitleDatePubMed
Reduction of the severity of nephropathy in aging Fischer 344 rats treated with analogs of arylsulfonyluria.
1979 Jul
Tolazamide-induced cholestasis.
1980 Aug
Potentiation of insulin action by a sulfonylurea in primary cultures of hepatocytes from normal and diabetic rats.
1983 Mar
Wernicke's encephalopathy induced by tolazamide.
1983 Sep 8
A case of chronic liver disease due to tolazamide.
1985 Jul
Transketolase abnormality in tolazamide-induced Wernicke's encephalopathy.
1986 Nov
Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor.
1995 Nov 17
Screening, library-assisted identification and validated quantification of oral antidiabetics of the sulfonylurea-type in plasma by atmospheric pressure chemical ionization liquid chromatography-mass spectrometry.
2002 Jun 15
[A 50-year history of new drugs in Japan-the development and progress of anti-diabetic drugs and the epidemiological aspects of diabetes mellitus].
2003
Selection of drugs to test the specificity of the Tg.AC assay by screening for induction of the gadd153 promoter in vitro.
2003 Aug
Barriers to self-monitoring of blood glucose among adults with diabetes in an HMO: a cross sectional study.
2003 Mar 19
Efficacy of sulfonylureas with insulin in type 2 diabetes mellitus.
2003 Nov
Detection of anti-diabetics in equine plasma and urine by liquid chromatography-tandem mass spectrometry.
2004 Nov 5
Cardiovascular risk factors associated with insulin resistance: effects of oral antidiabetic agents.
2005
Effects of sulfonylureas, alpha-endosulfine counterparts, on glomerulosclerosis in type 1 and type 2 models of diabetes.
2005 Feb
Metformin, sulfonylureas, or other antidiabetes drugs and the risk of lactic acidosis or hypoglycemia: a nested case-control analysis.
2008 Nov
Prediction of pharmacological and xenobiotic responses to drugs based on time course gene expression profiles.
2009 Dec 2
Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database.
2009 Dec 3
The second-meal phenomenon in type 2 diabetes.
2009 Jul
Accuracy of Veterans Affairs databases for diagnoses of chronic diseases.
2009 Oct
A review of exenatide as adjunctive therapy in patients with type 2 diabetes.
2009 Sep 21
Glucose biosensors: an overview of use in clinical practice.
2010
Epac2: a sulfonylurea receptor?
2012 Feb
Patents

Sample Use Guides

In Vivo Use Guide
The usual starting dose of Tolinase Tablets (Tolazamide) for the mild to moderately severe Type II diabetic patient is 100–250 mg daily administered with breakfast or the first main meal. Generally, if the fasting blood glucose is less than 200 mg/dl, the starting dose is 100 mg/day as a single daily dose. If the fasting blood glucose value is greater than 200 mg/dl, the starting dose is 250 mg/day as a single dose. If the patient is malnourished, underweight, elderly, or not eating properly, the initial therapy should be 100 mg once a day.
Route of Administration: Oral
In Vitro Use Guide
Tolazamide (1 mM) block contractions induced by prostaglandin F2alpha and the thromboxane A2 mimetic U-46619 in rat aorta
Substance Class Chemical
Created
by admin
on Fri Jun 25 20:56:37 UTC 2021
Edited
by admin
on Fri Jun 25 20:56:37 UTC 2021
Record UNII
9LT1BRO48Q
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TOLAZAMIDE
HSDB   INN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
INN   USAN  
Official Name English
TOLAZAMIDE [USAN]
Common Name English
TOLAZAMIDE [USP-RS]
Common Name English
BENZENESULFONAMIDE, N-(((HEXAHYDRO-1H-AZEPIN-1-YL)AMINO)CARBONYL)-4-METHYL-
Systematic Name English
TOLAZAMIDE [HSDB]
Common Name English
TOLAZAMIDE [MART.]
Common Name English
TOLAZAMIDE [MI]
Common Name English
TOLBUTAMIDE IMPURITY C [EP]
Common Name English
TOLAZAMIDE [WHO-DD]
Common Name English
TOLAZAMIDE [INN]
Common Name English
TOLAZAMIDE [VANDF]
Common Name English
U-17835
Code English
TOLAZAMIDE [ORANGE BOOK]
Common Name English
1-(HEXAHYDRO-1H-AZEPIN-1-YL)-3-(P-TOLYLSULFONYL)UREA
Common Name English
TOLAZAMIDE [USP MONOGRAPH]
Common Name English
TOLINASE
Brand Name English
NSC-70762
Code English
Classification Tree Code System Code
NCI_THESAURUS C97936
Created by admin on Fri Jun 25 20:56:37 UTC 2021 , Edited by admin on Fri Jun 25 20:56:37 UTC 2021
WHO-VATC QA10BB05
Created by admin on Fri Jun 25 20:56:37 UTC 2021 , Edited by admin on Fri Jun 25 20:56:37 UTC 2021
NDF-RT N0000008054
Created by admin on Fri Jun 25 20:56:37 UTC 2021 , Edited by admin on Fri Jun 25 20:56:37 UTC 2021
NDF-RT N0000008054
Created by admin on Fri Jun 25 20:56:37 UTC 2021 , Edited by admin on Fri Jun 25 20:56:37 UTC 2021
NDF-RT N0000175608
Created by admin on Fri Jun 25 20:56:37 UTC 2021 , Edited by admin on Fri Jun 25 20:56:37 UTC 2021
WHO-ATC A10BB05
Created by admin on Fri Jun 25 20:56:37 UTC 2021 , Edited by admin on Fri Jun 25 20:56:37 UTC 2021
LIVERTOX 975
Created by admin on Fri Jun 25 20:56:37 UTC 2021 , Edited by admin on Fri Jun 25 20:56:37 UTC 2021
NDF-RT N0000008054
Created by admin on Fri Jun 25 20:56:37 UTC 2021 , Edited by admin on Fri Jun 25 20:56:37 UTC 2021
Code System Code Type Description
WIKIPEDIA
Tolazamide
Created by admin on Fri Jun 25 20:56:37 UTC 2021 , Edited by admin on Fri Jun 25 20:56:37 UTC 2021
PRIMARY
NCI_THESAURUS
C29502
Created by admin on Fri Jun 25 20:56:37 UTC 2021 , Edited by admin on Fri Jun 25 20:56:37 UTC 2021
PRIMARY
LACTMED
Tolazamide
Created by admin on Fri Jun 25 20:56:37 UTC 2021 , Edited by admin on Fri Jun 25 20:56:37 UTC 2021
PRIMARY
MESH
D014042
Created by admin on Fri Jun 25 20:56:37 UTC 2021 , Edited by admin on Fri Jun 25 20:56:37 UTC 2021
PRIMARY
USP_CATALOG
1668001
Created by admin on Fri Jun 25 20:56:37 UTC 2021 , Edited by admin on Fri Jun 25 20:56:37 UTC 2021
PRIMARY USP-RS
EVMPD
SUB11147MIG
Created by admin on Fri Jun 25 20:56:37 UTC 2021 , Edited by admin on Fri Jun 25 20:56:37 UTC 2021
PRIMARY
IUPHAR
6847
Created by admin on Fri Jun 25 20:56:37 UTC 2021 , Edited by admin on Fri Jun 25 20:56:37 UTC 2021
PRIMARY
ECHA (EC/EINECS)
214-588-3
Created by admin on Fri Jun 25 20:56:37 UTC 2021 , Edited by admin on Fri Jun 25 20:56:37 UTC 2021
PRIMARY
RXCUI
10633
Created by admin on Fri Jun 25 20:56:37 UTC 2021 , Edited by admin on Fri Jun 25 20:56:37 UTC 2021
PRIMARY RxNorm
PUBCHEM
5503
Created by admin on Fri Jun 25 20:56:37 UTC 2021 , Edited by admin on Fri Jun 25 20:56:37 UTC 2021
PRIMARY
MERCK INDEX
M10935
Created by admin on Fri Jun 25 20:56:37 UTC 2021 , Edited by admin on Fri Jun 25 20:56:37 UTC 2021
PRIMARY Merck Index
DRUG CENTRAL
2694
Created by admin on Fri Jun 25 20:56:37 UTC 2021 , Edited by admin on Fri Jun 25 20:56:37 UTC 2021
PRIMARY
FDA UNII
9LT1BRO48Q
Created by admin on Fri Jun 25 20:56:37 UTC 2021 , Edited by admin on Fri Jun 25 20:56:37 UTC 2021
PRIMARY
HSDB
3192
Created by admin on Fri Jun 25 20:56:37 UTC 2021 , Edited by admin on Fri Jun 25 20:56:37 UTC 2021
PRIMARY
EPA CompTox
1156-19-0
Created by admin on Fri Jun 25 20:56:37 UTC 2021 , Edited by admin on Fri Jun 25 20:56:37 UTC 2021
PRIMARY
INN
1296
Created by admin on Fri Jun 25 20:56:37 UTC 2021 , Edited by admin on Fri Jun 25 20:56:37 UTC 2021
PRIMARY
ChEMBL
CHEMBL817
Created by admin on Fri Jun 25 20:56:37 UTC 2021 , Edited by admin on Fri Jun 25 20:56:37 UTC 2021
PRIMARY
CAS
1156-19-0
Created by admin on Fri Jun 25 20:56:37 UTC 2021 , Edited by admin on Fri Jun 25 20:56:37 UTC 2021
PRIMARY
DRUG BANK
DB00839
Created by admin on Fri Jun 25 20:56:37 UTC 2021 , Edited by admin on Fri Jun 25 20:56:37 UTC 2021
PRIMARY
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