GLIMEPIRIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H34N4O5S
Molecular Weight	490.616
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCC1=C(C)CN(C(=O)NCCC2=CC=C(C=C2)S(=O)(=O)NC(=O)N[C@H]3CC[C@H](C)CC3)C1=O

InChI

InChIKey=WIGIZIANZCJQQY-RUCARUNLSA-N

InChI=1S/C24H34N4O5S/c1-4-21-17(3)15-28(22(21)29)24(31)25-14-13-18-7-11-20(12-8-18)34(32,33)27-23(30)26-19-9-5-16(2)6-10-19/h7-8,11-12,16,19H,4-6,9-10,13-15H2,1-3H3,(H,25,31)(H2,26,27,30)/t16-,19-

HIDE SMILES / InChI

Molecular Formula	C24H34N4O5S
Molecular Weight	490.616
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.drugbank.ca/drugs/DB00222
Curator's Comment: Description was created based on several sources, including https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020496s021lbl.pdf

Glimepiride, like glyburide and glipizide, is a "second-generation" sulfonylurea agents. Glimepiride is used with diet to lower blood glucose by increasing the secretion of insulin from pancreas and increasing the sensitivity of peripheral tissues to insulin. The mechanism of action of glimepiride in lowering blood glucose appears to be dependent on stimulating the release of insulin from functioning pancreatic beta cells, and increasing sensitivity of peripheral tissues to insulin. Glimepiride likely binds to ATP-sensitive potassium channel receptors on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Membrane depolarization stimulates calcium ion influx through voltage-sensitive calcium channels. This increase in intracellular calcium ion concentration induces the secretion of insulin. Glimepiride is used for concomitant use with insulin for the treatment of noninsulin-dependent (type 2) diabetes mellitus. Glimepiride`s original trade name is Amaryl.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Acetylcholinesterase 209 Target ID: CHEMBL220 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26886763	Inhibitor 8504	235.0 µM [IC50]
Cytochrome P450 2C9 50 Target ID: CHEMBL3397 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26569597	Inhibitor 8504	12.7 µM [IC50]
ATP-sensitive inward rectifier potassium channel 1 7 Target ID: CHEMBL1293292 Sources: http://www.drugbank.ca/drugs/DB00222	Inhibitor 8504
Sulfonylurea receptor 1 5 Target ID: CHEMBL2071 Sources: http://www.drugbank.ca/drugs/DB00222	Agonist 2752	3.0 nM [IC50]
Potassium channel, inwardly rectifying, subfamily J, member 11 1 Target ID: CHEMBL1886 Sources: http://www.drugbank.ca/drugs/DB00222	Inhibitor 8504	400.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Type 2 diabetes mellitus 262 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020496s021lbl.pdf	Primary		Approved 8583	AMARYL Approved Use AMARYL is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus Launch Date 1999

C_max

Value	Dose	Co-administered	Analyte	Population
551 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/020496s015lbl.pdf	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:		GLIMEPIRIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
74.05 μg/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/20685507	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		GLIMEPIRIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
646.98 μg × h/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/20685507	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		GLIMEPIRIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
5.3 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/020496s015lbl.pdf	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:		GLIMEPIRIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
4.08 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/20685507	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		GLIMEPIRIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/020496s015lbl.pdf	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:		GLIMEPIRIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	substrate 1193		inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
UGT1A1 246 UGT1A3 89 UGT1A6 136 UGT1A9 148 UGT2B7 197 UGT2B15 84	OATP1B1 503

Drug as perpetrator

Target	Modality	Activity
UGT1A1 303	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22957438/	yes [Inhibition 100 uM]
UGT1A3 99	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22957438/	yes [Inhibition 100 uM]
UGT1A6 171	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22957438/	yes [Inhibition 100 uM]
UGT1A9 155	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22957438/	yes [Inhibition 100 uM]
UGT2B15 84	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22957438/	yes [Inhibition 100 uM]
UGT2B7 210	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22957438/	yes [Inhibition 100 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
OATP1B1 503	substrate 4014 Sources: https://www.nature.com/articles/s41598-018-29351-4	yes
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020496s029lbl.pdf; https://pubmed.ncbi.nlm.nih.gov/16325295/#:~:text=Glimepiride%2C%20a%20sulfonylurea%20hypoglycemic%20agent,known%20to%20have%20genetic%20polymorphisms.&text=The%20intrinsic%20clearance%20of%20glimepiride,by%20the%20CYP2C9*1%20enzyme.	yes		likely (co-administration study) Comment: Fluconazole may inhibit the metabolism of glimepiride, causing increased plasma concentrations of glimepiride which may lead to hypoglycemia. Rifampin may induce the metabolism of glimepiride, causing decreased plasma concentrations of glimepiride which may lead to worsening glycemic control; pharmacogenomic studies performed Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020496s029lbl.pdf; https://pubmed.ncbi.nlm.nih.gov/16325295/#:~:text=Glimepiride%2C%20a%20sulfonylurea%20hypoglycemic%20agent,known%20to%20have%20genetic%20polymorphisms.&text=The%20intrinsic%20clearance%20of%20glimepiride,by%20the%20CYP2C9*1%20enzyme.

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://febs.onlinelibrary.wiley.com/doi/full/10.1016/S0014-5793%2898%2901444-6?sid=nlm%3Apubmed

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:5383	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:5383
ChemicalBook	CB8275358	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8275358
ChemicalBook	CB8318552	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8318552
MolPort	MolPort-003-847-587	https://www.molport.com/shop/molecule-link/MolPort-003-847-587
Selleck Chemicals	Glimepiride	http://www.selleckchem.com/products/Glimepiride.html
ZINC	ZINC000100070954	http://zinc15.docking.org/substances/ZINC000100070954

PubMed

Title	Date	PubMed
Prevention of weight gain in type 2 diabetes requiring insulin treatment.	2004-03	14746576
Long-acting sulfonylureas -- long-acting hypoglycaemia.	2004-01-19	14723592
Determination of glimepiride in human plasma by liquid chromatography-electrospray ionization tandem mass spectrometry.	2004-01-05	14659441
Glimepiride pharmacokinetics in obese versus non-obese diabetic patients.	2004-01	14742789
Protective actions of gliclazide on high insulin-enhanced neutrophil-endothelial cell interactions through inhibition of mitogen activated protein kinase and protein kinase C pathways.	2004-01	14709397
The influence of glimepiride on the binding kinetics of insulin with its skeletal muscle and liver receptors in rats with short term and prolonged hyperglycemia induced by streptozotocin.	2004-01	14704628
Comparison of the effects of glimepiride and glibenclamide on adipose tissue tumour necrosis factor-alpha mRNA expression and cellularity.	2004-01	14686960
Hormonal counterregulation and consecutive glimepiride serum concentrations during severe hypoglycaemia associated with glimepiride therapy.	2003-12	14634699
Glimepiride and serum adiponectin level in type 2 diabetic subjects: response to Nagasaka et al.	2003-12	14633838
Change in patients' body weight after 12 months of treatment with glimepiride or glibenclamide in Type 2 diabetes: a multicentre retrospective cohort study.	2003-12	14600814
Study of glimepiride-b-cyclodextrin complex.	2003-11	14971307
Lichenoid drug eruption as a result of the recently released sulfonylurea glimepiride.	2003-11	14616504
The influence of glimepiride on the oxidative state of rats with streptozotocin-induced hyperglycemia.	2003-11	14586267
Efficacy of sulfonylureas with insulin in type 2 diabetes mellitus.	2003-11	14565810
Design of the cooperative study on glycemic control and complications in diabetes mellitus type 2: Veterans Affairs Diabetes Trial.	2003-10-30	14583175
A diabetic woman with worsening heart failure, hunger, and tremor.	2003-10	14621233
Risk of hypoglycaemia with oral antidiabetic agents in patients with Type 2 diabetes.	2003-10	14614647
Prospective multicentre trial comparing the efficacy of, and compliance with, glimepiride or acarbose treatment in patients with type 2 diabetes not controlled with diet alone.	2003-08	14768770
Effects of glimepiride on HbA(1c) and body weight in Type 2 diabetes: results of a 1.5-year follow-up study.	2003-07	12849919
Effect of glimepiride on serum adiponectin level in subjects with type 2 diabetes.	2003-07	12832345
Glimepiride reduces mononuclear activation of the redox-sensitive transcription factor nuclear factor-kappa B.	2003-07	12795658
Summaries for patients. A comparison of three insulin regimens (morning glargine, bedtime glargine, or bedtime neutral protamine Hagedorn) in addition to a pill for treating type 2 diabetes.	2003-06-17	12809480
Glimepiride combined with morning insulin glargine, bedtime neutral protamine hagedorn insulin, or bedtime insulin glargine in patients with type 2 diabetes. A randomized, controlled trial.	2003-06-17	12809451
Lispro insulin and metformin versus other combination in the diabetes mellitus type 2 management after secondary oral antidiabetic drug failure.	2003-06	12974145
Sulfonylureas and cardiovascular effects: from experimental data to clinical use. Available data in humans and clinical applications.	2003-06	12909809
Comparison of the micro- and macro-vascular effects of glimepiride and gliclazide in metformin-treated patients with Type 2 diabetes: a double-blind, crossover study.	2003-06	12814458
Characteristics and time course of severe glimepiride- versus glibenclamide-induced hypoglycaemia.	2003-06	12698302
Pitfalls in endosonographic imaging of suspected insulinomas: pancreatic nodules of unknown dignity.	2003-05	12720536
Combined bedtime insulin--daytime sulphonylurea regimen compared with two different daily insulin regimens in type 2 diabetes: effects on HbA1c and hypoglycaemia rate--a randomised trial.	2003-04-04	12673783
Glimepiride treatment and IGF-I in adolescents with type 1 diabetes: a prospective, randomized, double-blind, placebo-controlled study.	2003-04	12663616
[Differences between oral antidiabetics].	2003-03-20	12693123
Differential selectivity of insulin secretagogues: mechanisms, clinical implications, and drug interactions.	2003-03-08	12623163
Effects of sulfonylureas on K(ATP) channel-dependent vasodilation.	2003-03-08	12623162
Glimepiride in type 2 diabetes mellitus: a review of the worldwide therapeutic experience.	2003-03	12852703
The mechanisms underlying the unique pharmacodynamics of nateglinide.	2003-03	12652357
Comparison between repaglinide and glimepiride in patients with type 2 diabetes mellitus: a one-year, randomized, double-blind assessment of metabolic parameters and cardiovascular risk factors.	2003-02	12749508
Differential effects of sulphonylureas on the vasodilatory response evoked by K(ATP) channel openers.	2003-02	12588631
Impairment of myocardial protection in type 2 diabetic patients.	2003-02	12574175
Efficacy and safety profile of glimepiride in Mexican American Patients with type 2 diabetes mellitus: a randomized, placebo-controlled study.	2003-01	12637120
[Glimepiride in daily practice].	2003	14974179
[A 50-year history of new drugs in Japan-the development and progress of anti-diabetic drugs and the epidemiological aspects of diabetes mellitus].	2003	14570054
A flaw in the use of sulfonylurea screening to diagnose sulfonylurea overdosages.	2003	12828830
Inadvertent sulfonylurea overdosage and hypoglycemia in an elderly woman: failure of serum hypoglycemia screening.	2003	12828829
[Glimepiride--an oral antidiabetic agent].	2003	12822388
[Sulfonylurea receptors and their interaction with glimepiride].	2003	12774471
[Fear of the injection must not be an argument. Every second type 2 diabetic patient needs insulin].	2002-12-05	12577748
[Molecular mechanisms of insulin secretion].	2002-12	12703060
Immunoreactive insulin response to a single dose of glimepiride in lean type 2 diabetic subjects.	2002-10	12568204
Amaryl (glimepiride) in patients with type 2 diabetes mellitus.	2002	12580525
[Progress in studies on antidiabetic agents].	2001-09	12580115

Patents

Sample Use Guides

In Vivo Use Guide

The usual starting dose of AMARYL as initial therapy is 1-2 mg once daily, administered with breakfast or the first main meal. Those patients who may be more sensitive to hypoglycemic drugs should be started at 1 mg once daily, and should be titrated carefully.

Route of Administration: Oral

In Vitro Use Guide

Therapeutic concentrations of glimepiride (10 uM) block three types of recombinant KATP channel ± Kir6.2/SUR1, Kir6.2/SUR2A and Kir6.2/SUR2B (corresponding to the b-cell, cardiac and smooth muscle types of KATP channel)

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:11:07 GMT 2025` Edited by `admin` on `Mon Mar 31 18:11:07 GMT 2025`
Record UNII	6KY687524K
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

GLIMEPIRIDE

Official Name

English

DUETACT COMPONENT GLIMEPIRIDE

Preferred Name

English

Glimepiride [WHO-DD]

Common Name

English

GLIMEPIRIDE [ORANGE BOOK]

Common Name

English

AMARYL

Brand Name

English

GLIMEPIRIDE [USP-RS]

Common Name

English

GLIMEPIRIDE [MI]

Common Name

English

GLIMEPIRIDE [EP MONOGRAPH]

Common Name

English

GLIMEPIRIDE [USP IMPURITY]

Common Name

English

HOE 490

Code

English

NSC-759809

Code

English

GLIMEPIRIDE [USP MONOGRAPH]

Common Name

English

GLIMEPIRIDE [MART.]

Common Name

English

glimepiride [INN]

Common Name

English

GLIMEPIRIDE [VANDF]

Common Name

English

1H-PYRROLE-1-CARBOXAMIDE, 3-ETHYL-2,5-DIHYDRO-4-METHYL-N-(2-(4-(((((4-METHYLCYCLOHEXYL)AMINO)CARBONYL)AMINO)SULFONYL)PHENYL)ETHYL)-2-OXO-, TRANS-

Common Name

English

GLIMEPIRIDE [USAN]

Common Name

English

GLIMEPIRIDE [JAN]

Common Name

English

GLIMEPIRIDE [EMA EPAR]

Common Name

English

1-((P-(2-(3-ETHYL-4-METHYL-2-OXO-3-PYRROLINE-1-CARBOXAMIDO)ETHYL)PHENYL)SULFONYL)-3-(TRANS-4-METHYLCYCLOHEXYL)UREA

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000008054