TOLBUTAMIDE

US Previously Marketed

First approved in 1957

Details

Stereochemistry	ACHIRAL
Molecular Formula	C12H18N2O3S
Molecular Weight	270.348
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1

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

Description
Sources: http://www.drugbank.ca/drugs/DB01124
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
K-ATP channels, Rattus norvegicus 2 Target ID: K-ATP channels, Rattus norvegicus Sources: https://www.ncbi.nlm.nih.gov/pubmed/11523905	Inhibitor 8297		0.8 µM [IC50]
Sulfonylurea receptor 1, Kir6.2 13 Target ID: CHEMBL2096972 Sources: http://www.drugbank.ca/drugs/DB01124	Inhibitor 8297		1.15 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Type 2 diabetes mellitus 259 Sources: https://www.drugs.com/dosage/tolbutamide.html	Primary		Approved 8429	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 1989

C_max

Value	Dose	Co-administered	Analyte	Population
51.1 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9021442/	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

Value	Dose	Co-administered	Analyte	Population
998.42 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9021442/	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
418 min EXPERIMENT https://link.springer.com/article/10.1007%2FBF00614021	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
5% EXPERIMENT https://link.springer.com/article/10.1007%2FBF00614021	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

CYP3A4	CYP2C9	CYP2D6	hERG
	substrate 1037

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
UGT2B10 25 UGT1A6 108 UGT2B7 146 UGT1A1 204 UGT1A4 77 OATP1B1 788	CYP2C19 991 OAT2 115 P-gp 1537

Drug as perpetrator

Target	Modality	Activity
OATP1B1 803	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23248200/ Page: 8.0	not significant [IC50 >100 uM]
UGT1A6 141	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20939765/ Page: 7.0	weak [IC50 281 uM]
UGT1A1 254	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20939765/ Page: 7.0	weak [IC50 >300 uM]
UGT1A4 80	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20939765/ Page: 7.0	weak [IC50 >300 uM]
UGT2B10 27	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20939765/ Page: 7.0	weak [IC50 >300 uM]
UGT2B7 157	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20939765/ Page: 7.0	weak [IC50 >300 uM]

Drug as victim

Target	Modality	Activity
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9811164/	no
CYP2C19 991	substrate 3367 Sources: https://dmd.aspetjournals.org/content/28/3/354.long	yes
CYP2C9 1037	substrate 3367 Sources: https://dmd.aspetjournals.org/content/28/3/354.long	yes
OAT2 115	substrate 3367 Sources: https://jpet.aspetjournals.org/content/jpet/early/2018/01/11/jpet.117.245951.full.pdf?with-ds=yes#page=3 Page: 3.0	yes

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY564984	https://www.001chemical.com/chem/64-77-7
3B Scientific (Wuhan) Corp	3B2-0418	http://www.3bsc.com/index/pro_info.php?id=19774
AA Blocks	AA00E9FG	http://www.aablocks.com/goods/Goods/detail?id=AA00E9FG
AHH Chemical co.,ltd	API-1399	http://www.ahhchemical.com/product/API-1399.html
AK Scientific, Inc. (AKSCI)	J10018	http://www.aksci.com/item_detail.php?cat=J10018
AK Scientific, Inc. (AKSCI)	K045	http://www.aksci.com/item_detail.php?cat=K045
Aaron Chemicals	AR00EA78	http://www.aaronchem.com/64-77-7
AbMole Bioscience	M3077	http://www.abmole.com/products/tolbutamide.html
Acadechem	ACDS-029217	http://www.acadechemical.com/product/103916
Achemo Scientific Limited	AC-14868	http://www.achemo.com/product_view.asp?ID=4758
Alfa Aesar	B21698	https://www.alfa.com/en/catalog/B21698/
Alfa Chemistry	AP64777-A	https://reagents.alfa-chemistry.com/product/tolbutamide-cas-64-77-7-14588.html
Alfa Chemistry	AP64777-B	https://reagents.alfa-chemistry.com/product/tolbutamide-cas-64-77-7-14589.html
Allbio Pharm Co., Ltd	AD02724	http://www.allbiopharm.com/product/n/AD02724
Alsachim	2985	http://www.alsachim.com/product-C4057-glo.bal-view.html
ApexBio Technology	B2194	http://www.apexbt.com/tolbutamide-28680.html
Ark Pharm	AK115688	http://www.arkpharminc.com/products/64-77-7.html
Aurum Pharmatech LLC	NE30724	http://www.Aurumpharmatech.com/Product/ProductDetails/NE30724
Avantor Inc	101096-316	https://us.vwr.com/store/catalog/product.jsp?catalog_number=101096-316
BLD Pharm	BD154332	http://www.bldpharm.com/products/64-77-7.html
BenchChem	B545540	https://www.benchchem.com/product/b545540
BioChemPartner	BCP09192	http://www.biochempartner.com/64-77-7-BCP09192
BioCrick	BCC5001	http://www.biocrick.com/Tolbutamide-BCC5001.html
BioSynth	W-104820	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/W-104820.html
CSNpharm	CSN12105	https://www.csnpharm.com/products/tolbutamide.html
Capot Chemical	18102	http://www.capotchem.com/en/18102.htm
Capot Chemical	PubChem18102	http://www.capotchem.com/en/18102.htm
Chem Scene	CS-2500	http://www.chemscene.com/64-77-7.html
ChemMol	30102245	http://www.chemmol.com/chemmol/30102245.html
ChemMol	49410146	http://www.chemmol.com/chemmol/49410146.html
Chemspace	CSSB00000696203	https://chem-space.com/CSSB00000696203
Clearsynth	CS-T-44523	https://www.clearsynth.com/en/CST44523.html
DC Chemicals	DC9023	http://www.dcchemicals.com/product_show-Tolbutamide.html
Debye Scientific	DB-054728	http://www.debyesci.com/cas_64-77-7.html
Enamine	Z44591715	https://www.enaminestore.com/catalog/Z44591715
Finetech	FT-0603265	http://www.finetechnology-ind.com/prod/detail/pub/64-77-7.html
Glentham Life Sciences	GP0797	http://www.glentham.com/products/product/GP0797/
Hairui	HR124945	http://www.hairuichem.com/en/product/64-77-7.html
LGC Standards	DRE-C17589900	https://www.lgcstandards.com/US/en/p/DRE-C17589900
LGC Standards	LGCAMP1089.00-11	https://www.lgcstandards.com/US/en/p/LGCAMP1089.00-11
LGC Standards	LGCFOR1089.00	https://www.lgcstandards.com/US/en/p/LGCFOR1089.00
LGC Standards	MM1089.00	https://www.lgcstandards.com/US/en/p/MM1089.00
Lab Network	LN00235930	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00235930
MedChem Express	HY-B0401	https://www.medchemexpress.com/Tolbutamide.html
Molcore	MC564984	https://www.molcore.com/product/64-77-7
MuseChem	I004440	https://www.musechem.com/product/I004440.html
Oakwood	47218	http://www.oakwoodchemical.com/ProductsList.aspx?CategoryID=-2&txtSearch=41080&ExtHyperLink=1
Selleck Chemicals	S2443	http://www.selleckchem.com/products/tolbutamide.html
Sigma-Aldrich	46968_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/46968?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	T0891_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/t0891?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	T1700000_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/t1700000?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	1670003_USP	https://www.sigmaaldrich.com/catalog/product/usp/1670003?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sinfoo Biotech	S013560	http://www.sinfoobiotech.com/product/1016958
Smolecule	S545540	http://www.smolecule.com/products/s545540
THE BioTek	bt-285914	https://www.thebiotek.com/product/inhibitors/bt-285914
VladaChem	VL144721	https://www.vladachem.com/product.php?products=64-77-7
VladaChem	VL271328-100G	https://www.vladachem.com/product.php?products=64-77-7
abcr GmbH	AB132954	http://www.abcr.com/shop/en/AB132954
mcule	MCULE-9720356859	https://mcule.com/MCULE-9720356859/

PubMed

Title	Date	PubMed
Minipig cytochrome P450 3A, 2A and 2C enzymes have similar properties to human analogs.	2001	11737866
Effects of nicorandil administration on survival rate and arrhythmias during reperfusion in anesthetized rabbits.	2001	11598418
Phorbol ester impairs electrical excitation of rat pancreatic beta-cells through PKC-independent activation of KATP channels.	2001	11560763
Drug interactions with irbesartan.	2001	11523726
Effects of vitamins and common drugs on reduction of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in rat microsomes.	2001 Apr	11780779
The enhancement of glucose uptake caused by the collapse of gap junction communication is due to an increase in astrocyte proliferation.	2001 Aug	11520909
Sulfonylurea receptors inhibit the epithelial sodium channel (ENaC) by reducing surface expression.	2001 Aug	11512032
An ATP-sensitive K(+) conductance in dissociated neurones from adult rat intracardiac ganglia.	2001 Aug 1	11483702
Identification of a null allele of CYP2C9 in an African-American exhibiting toxicity to phenytoin.	2001 Dec	11740344
Phenotyping of individual pancreatic islets locates genetic defects in stimulus secretion coupling to Niddm1i within the major diabetes locus in GK rats.	2001 Dec	11723056
Opioid receptor modulation of a metabolically sensitive ion channel in rat amygdala neurons.	2001 Dec 1	11717342
Desensitization of insulin secretory response to imidazolines, tolbutamide, and quinine. II. Electrophysiological and fluorimetric studies.	2001 Dec 15	11755123
Desensitization of insulin secretory response to imidazolines, tolbutamide, and quinine. I. Secretory and morphological studies.	2001 Dec 15	11755122
Proliferation of C6 glioma cells is blunted by the increase in gap junction communication caused by tolbutamide.	2001 Dec 7	11741589
Effects of CYP2C19 genotype and CYP2C9 on fluoxetine N-demethylation in human liver microsomes.	2001 Jan	11730569
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	11548862
Influence of the preparation method on the physicochemical properties of tolbutamide/cyclodextrin binary systems.	2001 Jul	11548859
Swelling-induced changes in cytosolic [Ca2++] in insulin-secreting cells: a role in regulatory volume decrease?	2001 Jul 5	11476951
Free radical-mediated tolbutamide desensitization of K+ATP channels in rat pancreatic beta-cells.	2001 Jun	11523905
Interindividual variations in levels and activities of cytochrome P-450 in liver microsomes of Chinese subjects.	2001 Mar	11742579
Hypoglycemic effect of Hibiscus rosa sinensis L. leaf extract in glucose and streptozotocin induced hyperglycemic rats.	2001 Mar	11495291
An aqueous extract of the green leafy vegetable Ipomoea aquatica is as effective as the oral hypoglycaemic drug tolbutamide in reducing the blood sugar levels of Wistar rats.	2001 Nov	11746851
In vitro evaluation of valproic acid as an inhibitor of human cytochrome P450 isoforms: preferential inhibition of cytochrome P450 2C9 (CYP2C9).	2001 Nov	11736863
Application of the PKCYP-test to predict the amount of in vivo CYP2C11 using tolbutamide as a probe.	2001 Nov	11725969
Monoclonal antibodies specific and inhibitory to human cytochromes P450 2C8, 2C9, and 2C19.	2001 Nov	11602516
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	11716850
In vitro cytochrome P450-mediated hepatic activities for five substrates in specific pathogen free chickens.	2001 Oct	11696084
Quantification of beta-cell function during IVGTT in Type II and non-diabetic subjects: assessment of insulin secretion by mathematical methods.	2001 Oct	11692185
Genetic variability of the SUR1 promoter in relation to beta-cell function and Type II diabetes mellitus.	2001 Oct	11692183
Clinical relevance of genetic polymorphisms in the human CYP2C subfamily.	2001 Oct	11678778
The effects of St John's wort (Hypericum perforatum) on human cytochrome P450 activity.	2001 Oct	11673747
Molecular modelling and 1H-NMR: ultimate tools for the investigation of tolbutamide: beta-cyclodextrin and tolbutamide: hydroxypropyl-beta-cyclodextrin complexes.	2001 Oct	11605649
Fasting glucose insulin ratio: a useful measure of insulin resistance in girls with premature adrenarche.	2001 Oct	11600513
Insulin activates ATP-sensitive K(+) channels in pancreatic beta-cells through a phosphatidylinositol 3-kinase-dependent pathway.	2001 Oct	11574397
Diabetogenic effect of cyclosporin A is mediated by interference with mitochondrial function of pancreatic B-cells.	2001 Oct	11562451
Effects of tolbutamide and N-benzoyl-D-phenylalanine (NBDP) on the regulation of [Ca2+]i oscillations in mouse pancreatic islets.	2001 Oct 1	11543727
Antidiabetic activity of the rhizoma of Anemarrhena asphodeloides and active components, mangiferin and its glucoside.	2001 Sep	11558559
Effect of Cirsium pascuarense on blood glucose levels of normoglycaemic and alloxan-diabetic mice.	2001 Sep	11536391
Dibutyryl-cyclic GMP induces peripheral antinociception via activation of ATP-sensitive K(+) channels in the rat PGE2-induced hyperalgesic paw.	2001 Sep	11522604
Adenosine-mediated inhibition of striatal GABAergic synaptic transmission during in vitro ischaemia.	2001 Sep	11522587
Functional characterization of rat organic anion transporter 2 in LLC-PK1 cells.	2001 Sep	11504818
Mechanism-based inactivation of CYP2C11 by diclofenac.	2001 Sep	11502726
ATP-independent anoxic activation of ATP-sensitive K+ channels in dorsal vagal neurons of juvenile mice in situ.	2002	11801367
Novel properties of peptides derived from the sequence coded by exon 26A of human elastin.	2002 Feb	11809415
Triterpenes from Agarista mexicana as potential antidiabetic agents.	2002 Feb	11807966
The effect of bergamottin on diazepam plasma levels and P450 enzymes in beagle dogs.	2002 Feb	11792681
S2' substrate specificity and the role of His110 and His111 in the exopeptidase activity of human cathepsin B.	2002 Feb 1	11802791
Carriers of an inactivating beta-cell ATP-sensitive K(+) channel mutation have normal glucose tolerance and insulin sensitivity and appropriate insulin secretion.	2002 Jan	11772909
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	11756328
Inhibition of glucose-induced electrical activity by 4-hydroxytamoxifen in rat pancreatic beta-cells.	2002 Jan	11747991

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

Insulin effects were eliminated in the presence of a ATP-dependent K+ (K(ATP)) channel antagonist tolbutamide (200 uM) in brain stem slices

Name

Type

Language

TOLBUTAMIDE

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

Tolbutamide [WHO-DD]

Common Name

English

TOLBUTAMIDUM [WHO-IP LATIN]

Common Name

English

NSC-23813

Code

English

ORINASE

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

TOLBUTAMIDE [JAN]

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