U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C12H18N2O3S
Molecular Weight 270.3495
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TOLBUTAMIDE

SMILES

CCCCN=C(NS(=O)(=O)c1ccc(C)cc1)O

InChI

InChIKey=JLRGJRBPOGGCBT-UHFFFAOYSA-N
InChI=1S/C12H18N2O3S/c1-3-4-9-13-12(15)14-18(16,17)11-7-5-10(2)6-8-11/h5-8H,3-4,9H2,1-2H3,(H2,13,14,15)

HIDE SMILES / InChI

Molecular Formula C12H18N2O3S
Molecular Weight 270.3495
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/tolbutamide.html

Tolbutamide is an oral antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It is structurally similar to acetohexamide, chlorpropamide and tolazamide and belongs to the sulfonylurea class of insulin secretagogues, which act by stimulating β cells of the pancreas to release insulin. Sulfonylureas lower blood glucose in patients with NIDDM by directly stimulating the acute release of insulin from functioning beta cells of pancreatic islet tissue by an unknown process that involves a sulfonylurea receptor (receptor 1) on the beta cell. Sulfonylureas inhibit the ATP-potassium channels on the beta cell membrane and potassium efflux, which results in depolarization and calcium influx, calcium-calmodulin binding, kinase activation, and release of insulin-containing granules by exocytosis, an effect similar to that of glucose.

CNS Activity

Curator's Comment:: Shown in rats and mice

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: K-ATP channels, Rattus norvegicus
0.8 µM [IC50]
1.15 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Tolbutamide

Approved Use

Tolbutamide tablets are indicated as an adjunct to diet to lower the blood glucose in patients with non-insulin-dependent diabetes mellitus (type II) whose hyperglycemia cannot be controlled by diet alone.

Launch Date

6.257952E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
51.1 μg/mL
1 g single, oral
dose: 1 g
route of administration: Oral
experiment type: SINGLE
co-administered:
TOLBUTAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
998.42 μg × h/mL
1 g single, oral
dose: 1 g
route of administration: Oral
experiment type: SINGLE
co-administered:
TOLBUTAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
418 min
20 mg/kg bw single, intravenous
dose: 20 mg/kg bw
route of administration: Intravenous
experiment type: SINGLE
co-administered:
TOLBUTAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
5%
20 mg/kg bw single, intravenous
dose: 20 mg/kg bw
route of administration: Intravenous
experiment type: SINGLE
co-administered:
TOLBUTAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
not significant [IC50 >100 uM]
weak [IC50 281 uM]
weak [IC50 >300 uM]
weak [IC50 >300 uM]
weak [IC50 >300 uM]
weak [IC50 >300 uM]
Drug as victim
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Minipig cytochrome P450 3A, 2A and 2C enzymes have similar properties to human analogs.
2001
Effects of nicorandil administration on survival rate and arrhythmias during reperfusion in anesthetized rabbits.
2001
Phorbol ester impairs electrical excitation of rat pancreatic beta-cells through PKC-independent activation of KATP channels.
2001
Drug interactions with irbesartan.
2001
Effects of vitamins and common drugs on reduction of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in rat microsomes.
2001 Apr
Interaction of sulfonylurea-conjugated polymer with insulinoma cell line of MIN6 and its effect on insulin secretion.
2001 Apr
Relative contributions of CYP2C9 and 2C19 to phenytoin 4-hydroxylation in vitro: inhibition by sulfaphenazole, omeprazole, and ticlopidine.
2001 Apr
The enhancement of glucose uptake caused by the collapse of gap junction communication is due to an increase in astrocyte proliferation.
2001 Aug
Sulfonylurea receptors inhibit the epithelial sodium channel (ENaC) by reducing surface expression.
2001 Aug
An ATP-sensitive K(+) conductance in dissociated neurones from adult rat intracardiac ganglia.
2001 Aug 1
Identification of a null allele of CYP2C9 in an African-American exhibiting toxicity to phenytoin.
2001 Dec
Phenotyping of individual pancreatic islets locates genetic defects in stimulus secretion coupling to Niddm1i within the major diabetes locus in GK rats.
2001 Dec
Opioid receptor modulation of a metabolically sensitive ion channel in rat amygdala neurons.
2001 Dec 1
Desensitization of insulin secretory response to imidazolines, tolbutamide, and quinine. II. Electrophysiological and fluorimetric studies.
2001 Dec 15
Desensitization of insulin secretory response to imidazolines, tolbutamide, and quinine. I. Secretory and morphological studies.
2001 Dec 15
Proliferation of C6 glioma cells is blunted by the increase in gap junction communication caused by tolbutamide.
2001 Dec 7
Effects of CYP2C19 genotype and CYP2C9 on fluoxetine N-demethylation in human liver microsomes.
2001 Jan
The potential of small-scale fusion experiments and the Gordon-Taylor equation to predict the suitability of drug/polymer blends for melt extrusion.
2001 Jul
Influence of the preparation method on the physicochemical properties of tolbutamide/cyclodextrin binary systems.
2001 Jul
Longitudinal changes in body fat in African American and Caucasian children: influence of fasting insulin and insulin sensitivity.
2001 Jul
Swelling-induced changes in cytosolic [Ca2++] in insulin-secreting cells: a role in regulatory volume decrease?
2001 Jul 5
Establishment of the transformants expressing human cytochrome P450 subtypes in HepG2, and their applications on drug metabolism and toxicology.
2001 Jun
Interindividual variations in levels and activities of cytochrome P-450 in liver microsomes of Chinese subjects.
2001 Mar
Hypoglycemic effect of Hibiscus rosa sinensis L. leaf extract in glucose and streptozotocin induced hyperglycemic rats.
2001 Mar
Inhibition of human CYP1A2 activity in vitro by methylxanthines: potent competitive inhibition by 8-phenyltheophylline.
2001 Mar
Involvement of calmodulin in glucagon-like peptide 1(7-36) amide-induced inhibition of the ATP-sensitive K+ channel in mouse pancreatic beta-cells.
2001 May
In vitro evaluation of valproic acid as an inhibitor of human cytochrome P450 isoforms: preferential inhibition of cytochrome P450 2C9 (CYP2C9).
2001 Nov
Application of the PKCYP-test to predict the amount of in vivo CYP2C11 using tolbutamide as a probe.
2001 Nov
Monoclonal antibodies specific and inhibitory to human cytochromes P450 2C8, 2C9, and 2C19.
2001 Nov
The effects of mitiglinide (KAD-1229), a new anti-diabetic drug, on ATP-sensitive K+ channels and insulin secretion: comparison with the sulfonylureas and nateglinide.
2001 Nov 9
In vitro cytochrome P450-mediated hepatic activities for five substrates in specific pathogen free chickens.
2001 Oct
Quantification of beta-cell function during IVGTT in Type II and non-diabetic subjects: assessment of insulin secretion by mathematical methods.
2001 Oct
Genetic variability of the SUR1 promoter in relation to beta-cell function and Type II diabetes mellitus.
2001 Oct
The effects of St John's wort (Hypericum perforatum) on human cytochrome P450 activity.
2001 Oct
Fasting glucose insulin ratio: a useful measure of insulin resistance in girls with premature adrenarche.
2001 Oct
Insulin activates ATP-sensitive K(+) channels in pancreatic beta-cells through a phosphatidylinositol 3-kinase-dependent pathway.
2001 Oct
Diabetogenic effect of cyclosporin A is mediated by interference with mitochondrial function of pancreatic B-cells.
2001 Oct
Effects of tolbutamide and N-benzoyl-D-phenylalanine (NBDP) on the regulation of [Ca2+]i oscillations in mouse pancreatic islets.
2001 Oct 1
Antidiabetic activity of the rhizoma of Anemarrhena asphodeloides and active components, mangiferin and its glucoside.
2001 Sep
Effect of Cirsium pascuarense on blood glucose levels of normoglycaemic and alloxan-diabetic mice.
2001 Sep
Adenosine-mediated inhibition of striatal GABAergic synaptic transmission during in vitro ischaemia.
2001 Sep
Functional characterization of rat organic anion transporter 2 in LLC-PK1 cells.
2001 Sep
Mechanism-based inactivation of CYP2C11 by diclofenac.
2001 Sep
ATP-independent anoxic activation of ATP-sensitive K+ channels in dorsal vagal neurons of juvenile mice in situ.
2002
Novel properties of peptides derived from the sequence coded by exon 26A of human elastin.
2002 Feb
Triterpenes from Agarista mexicana as potential antidiabetic agents.
2002 Feb
The effect of bergamottin on diazepam plasma levels and P450 enzymes in beagle dogs.
2002 Feb
S2' substrate specificity and the role of His110 and His111 in the exopeptidase activity of human cathepsin B.
2002 Feb 1
Carriers of an inactivating beta-cell ATP-sensitive K(+) channel mutation have normal glucose tolerance and insulin sensitivity and appropriate insulin secretion.
2002 Jan
A key role for beta-cell cytosolic phospholipase A(2) in the maintenance of insulin stores but not in the initiation of insulin secretion.
2002 Jan
Patents

Sample Use Guides

Usual Adult Dose for Diabetes Type 2 Initial dose: 1 to 2 g orally once a day or in divided doses through the day -Adjust dose based on blood glucose response Maintenance dose: 0.25 to 3 g orally once a day or in divided doses through the day Maximum dose: 3 g per day
Route of Administration: Oral
Insulin effects were eliminated in the presence of a ATP-dependent K+ (K(ATP)) channel antagonist tolbutamide (200 uM) in brain stem slices
Substance Class Chemical
Created
by admin
on Fri Jun 25 20:55:00 UTC 2021
Edited
by admin
on Fri Jun 25 20:55:00 UTC 2021
Record UNII
982XCM1FOI
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TOLBUTAMIDE
EP   HSDB   INN   MART.   MI   ORANGE BOOK   USP   USP-RS   VANDF   WHO-DD   WHO-IP  
INN  
Official Name English
TOLBUTAMIDE [VANDF]
Common Name English
BUTAMIDE
Common Name English
TOLBUTAMIDE [EP MONOGRAPH]
Common Name English
TOLBUTAMIDE [INN]
Common Name English
1-BUTYL-3-(P-TOLYLSULFONYL)UREA
Common Name English
BENZENESULFONAMIDE, N-((BUTYLAMINO)CARBONYL)-4-METHYL-
Systematic Name English
TOLBUTAMIDE [MART.]
Common Name English
TOLBUTAMIDUM [WHO-IP LATIN]
Common Name English
NSC-23813
Code English
ORINASE
Common Name English
TOLBUTAMIDE [WHO-DD]
Common Name English
NSC-87833
Code English
TOLBUTAMIDE [MI]
Common Name English
ARKOZAL
Common Name English
TOLBUTAMIDE [HSDB]
Common Name English
GLYCONON
Common Name English
TOLBUTAMIDE [USP MONOGRAPH]
Common Name English
DIABETAMID
Common Name English
TOLBUTAMIDE [WHO-IP]
Common Name English
IPOGLICONE
Common Name English
WILLBUTAMIDE
Common Name English
TOLBUTAMIDE [USP-RS]
Common Name English
TOLBUTAMIDE [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
CFR 21 CFR 310.517
Created by admin on Fri Jun 25 20:55:00 UTC 2021 , Edited by admin on Fri Jun 25 20:55:00 UTC 2021
WHO-VATC QA10BB03
Created by admin on Fri Jun 25 20:55:01 UTC 2021 , Edited by admin on Fri Jun 25 20:55:01 UTC 2021
LIVERTOX 976
Created by admin on Fri Jun 25 20:55:01 UTC 2021 , Edited by admin on Fri Jun 25 20:55:01 UTC 2021
NDF-RT N0000008054
Created by admin on Fri Jun 25 20:55:01 UTC 2021 , Edited by admin on Fri Jun 25 20:55:01 UTC 2021
WHO-VATC QV04CA01
Created by admin on Fri Jun 25 20:55:01 UTC 2021 , Edited by admin on Fri Jun 25 20:55:01 UTC 2021
WHO-ATC A10BB03
Created by admin on Fri Jun 25 20:55:00 UTC 2021 , Edited by admin on Fri Jun 25 20:55:00 UTC 2021
WHO-ATC V04CA01
Created by admin on Fri Jun 25 20:55:00 UTC 2021 , Edited by admin on Fri Jun 25 20:55:00 UTC 2021
NDF-RT N0000175608
Created by admin on Fri Jun 25 20:55:01 UTC 2021 , Edited by admin on Fri Jun 25 20:55:01 UTC 2021
NDF-RT N0000008054
Created by admin on Fri Jun 25 20:55:01 UTC 2021 , Edited by admin on Fri Jun 25 20:55:01 UTC 2021
NDF-RT N0000008054
Created by admin on Fri Jun 25 20:55:01 UTC 2021 , Edited by admin on Fri Jun 25 20:55:01 UTC 2021
NCI_THESAURUS C97936
Created by admin on Fri Jun 25 20:55:01 UTC 2021 , Edited by admin on Fri Jun 25 20:55:01 UTC 2021
Code System Code Type Description
PUBCHEM
5505
Created by admin on Fri Jun 25 20:55:01 UTC 2021 , Edited by admin on Fri Jun 25 20:55:01 UTC 2021
PRIMARY
ECHA (EC/EINECS)
200-594-3
Created by admin on Fri Jun 25 20:55:01 UTC 2021 , Edited by admin on Fri Jun 25 20:55:01 UTC 2021
PRIMARY
MESH
D014044
Created by admin on Fri Jun 25 20:55:01 UTC 2021 , Edited by admin on Fri Jun 25 20:55:01 UTC 2021
PRIMARY
IUPHAR
6848
Created by admin on Fri Jun 25 20:55:01 UTC 2021 , Edited by admin on Fri Jun 25 20:55:01 UTC 2021
PRIMARY
WIKIPEDIA
TOLBUTAMIDE
Created by admin on Fri Jun 25 20:55:01 UTC 2021 , Edited by admin on Fri Jun 25 20:55:01 UTC 2021
PRIMARY
HSDB
3393
Created by admin on Fri Jun 25 20:55:01 UTC 2021 , Edited by admin on Fri Jun 25 20:55:01 UTC 2021
PRIMARY
MERCK INDEX
M10937
Created by admin on Fri Jun 25 20:55:01 UTC 2021 , Edited by admin on Fri Jun 25 20:55:01 UTC 2021
PRIMARY Merck Index
FDA UNII
982XCM1FOI
Created by admin on Fri Jun 25 20:55:01 UTC 2021 , Edited by admin on Fri Jun 25 20:55:01 UTC 2021
PRIMARY
ChEMBL
CHEMBL782
Created by admin on Fri Jun 25 20:55:00 UTC 2021 , Edited by admin on Fri Jun 25 20:55:00 UTC 2021
PRIMARY
EVMPD
SUB11150MIG
Created by admin on Fri Jun 25 20:55:00 UTC 2021 , Edited by admin on Fri Jun 25 20:55:00 UTC 2021
PRIMARY
LACTMED
Tolbutamide
Created by admin on Fri Jun 25 20:55:01 UTC 2021 , Edited by admin on Fri Jun 25 20:55:01 UTC 2021
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
TOLBUTAMIDE
Created by admin on Fri Jun 25 20:55:01 UTC 2021 , Edited by admin on Fri Jun 25 20:55:01 UTC 2021
PRIMARY Description: A white or almost white, crystalline powder; odourless or almost odourless. Solubility: Practically insoluble in water; soluble in 10 parts of ethanol (~750 g/l) TS; soluble in acetone R. Category: Antidiabetic. Storage: Tolbutamide should be kept in a tightly closed container, protected from light. Additional information: Even in the absence of light, Tolbutamide is gradually degraded on exposure to a humid atmosphere, the decomposition being faster at higher temperatures. Definition: Tolbutamide contains not less than 99.0% and not more than 101.0% of C12H18N2O3S, calculated with reference to the dried substance.
INN
602
Created by admin on Fri Jun 25 20:55:01 UTC 2021 , Edited by admin on Fri Jun 25 20:55:01 UTC 2021
PRIMARY
DRUG CENTRAL
2696
Created by admin on Fri Jun 25 20:55:00 UTC 2021 , Edited by admin on Fri Jun 25 20:55:00 UTC 2021
PRIMARY
USP_CATALOG
1670003
Created by admin on Fri Jun 25 20:55:01 UTC 2021 , Edited by admin on Fri Jun 25 20:55:01 UTC 2021
PRIMARY USP-RS
EPA CompTox
64-77-7
Created by admin on Fri Jun 25 20:55:01 UTC 2021 , Edited by admin on Fri Jun 25 20:55:01 UTC 2021
PRIMARY
RXCUI
10635
Created by admin on Fri Jun 25 20:55:01 UTC 2021 , Edited by admin on Fri Jun 25 20:55:01 UTC 2021
PRIMARY RxNorm
NCI_THESAURUS
C66610
Created by admin on Fri Jun 25 20:55:01 UTC 2021 , Edited by admin on Fri Jun 25 20:55:01 UTC 2021
PRIMARY
DRUG BANK
DB01124
Created by admin on Fri Jun 25 20:55:00 UTC 2021 , Edited by admin on Fri Jun 25 20:55:00 UTC 2021
PRIMARY
CAS
64-77-7
Created by admin on Fri Jun 25 20:55:00 UTC 2021 , Edited by admin on Fri Jun 25 20:55:00 UTC 2021
PRIMARY
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