TOLBUTAMIDE

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

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

Molecular Formula	C12H18N2O3S
Molecular Weight	270.348
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description

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	Inhibitor 8,297		0.8 µM [IC50]
Sulfonylurea receptor 1, Kir6.2 13	Inhibitor 8,297		1.15 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Type 2 diabetes mellitus 259	Primary		Approved 8,429	Tolbutamide

C_max

Value	Dose	Co-administered	Analyte	Population
51.1 μg/mL	1 g single, oral		TOLBUTAMIDE plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
998.42 μg × h/mL	1 g single, oral		TOLBUTAMIDE plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
418 min	20 mg/kg bw single, intravenous		TOLBUTAMIDE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
5%	20 mg/kg bw single, intravenous		TOLBUTAMIDE plasma	Homo sapiens

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	substrate 1,037

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 1,537

Drug as perpetrator

Show entries

Target	Modality	Activity
OATP1B1 803	inhibitor 3,277	not significant [IC50 >100 uM]
UGT1A6 141	inhibitor 3,277	weak [IC50 281 uM]
UGT1A1 254	inhibitor 3,277	weak [IC50 >300 uM]
UGT1A4 80	inhibitor 3,277	weak [IC50 >300 uM]
UGT2B10 27	inhibitor 3,277	weak [IC50 >300 uM]

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Drug as victim

Show entries

Target	Modality	Activity
P-gp 1,537	substrate 3,367	no
CYP2C19 991	substrate 3,367	yes
CYP2C9 1,037	substrate 3,367	yes
OAT2 115	substrate 3,367	yes

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Sourcing

Sourcing

Show entries

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

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PubMed

Show entries

Title	Date	PubMed
Stimulation of tolbutamide hydroxylation by acetone and acetonitrile in human liver microsomes and in a cytochrome P-450 2C9-reconstituted system.	2000 Jan	10611138
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
Clinical pharmacokinetics of fluvastatin.	2001	11368292

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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