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Details

Stereochemistry ACHIRAL
Molecular Formula C14H21N3O3S
Molecular Weight 311.4
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TOLAZAMIDE

SMILES

CC1=CC=C(C=C1)S(=O)(=O)NC(=O)NN2CCCCCC2

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

Description

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

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
5.861 nM [Ki]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Tolazamide

Cmax

ValueDoseCo-administeredAnalytePopulation
21.8 μg/mL
500 mg single, oral
TOLAZAMIDE serum
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
260 μg × h/mL
500 mg single, oral
TOLAZAMIDE serum
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
4.6 h
500 mg single, oral
TOLAZAMIDE serum
Homo sapiens

Doses

AEs

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as perpetrator​

Drug as victim

PubMed

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