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
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)
Molecular Formula | C14H21N3O3S |
Molecular Weight | 311.4 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionSources: http://www.drugbank.ca/drugs/DB00839Curator's Comment: Description was created based on several sources, including
https://www.drugs.com/pro/tolinase.html
Sources: http://www.drugbank.ca/drugs/DB00839
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
Sources: http://en.pharmacodia.com/web/drug/1_7746.html
Curator's Comment: was developed and marketed as Tolinase® by Pharmacia and Upjohn
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2096972 Sources: http://www.genome.jp/dbget-bin/www_bget?D00379 |
5.861 nM [Ki] | ||
Target ID: CHEMBL1293292 Sources: http://www.drugbank.ca/drugs/DB00839 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Tolazamide Approved UseIndicated 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 Date1984 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
21.8 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7175719/ |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
260 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7175719/ |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
4.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7175719/ |
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
Dose | Population | Adverse 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 |
|
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 Health Status: unhealthy Age Group: 59 Sex: F 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 Health Status: unhealthy Age Group: 62 Sex: F 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 Health Status: unhealthy Age Group: 69 Sex: F Sources: |
Other AEs: Dizziness... |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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 Health Status: unhealthy Age Group: 59 Sex: F 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 Health Status: unhealthy Age Group: 62 Sex: F 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 Health Status: unhealthy Age Group: 69 Sex: F Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/2661591/ |
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
major | ||||
minor |
PubMed
Title | Date | PubMed |
---|---|---|
Tolazamide-induced cholestasis. | 1980 Aug |
|
Wernicke's encephalopathy induced by tolazamide. | 1983 Sep 8 |
|
Prediction of pharmacological and xenobiotic responses to drugs based on time course gene expression profiles. | 2009 Dec 2 |
|
Glucose biosensors: an overview of use in clinical practice. | 2010 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/pro/tolinase.html
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9151937
Tolazamide (1 mM) block contractions induced by prostaglandin F2alpha and the thromboxane A2 mimetic U-46619 in rat aorta
Substance Class |
Chemical
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9LT1BRO48Q
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NCI_THESAURUS |
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N0000008054
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Tolazamide
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C29502
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Tolazamide
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m10935
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DB00839
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1668001
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CHROMATOGRAPHIC PURITY (HPLC/UV)
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