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

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 207 Target ID: CHEMBL220 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26886763	Inhibitor 8297	235.0 µM [IC50]
Cytochrome P450 2C9 50 Target ID: CHEMBL3397 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26569597	Inhibitor 8297	12.7 µM [IC50]
ATP-sensitive inward rectifier potassium channel 1 7 Target ID: CHEMBL1293292 Sources: http://www.drugbank.ca/drugs/DB00222	Inhibitor 8297
Sulfonylurea receptor 1 5 Target ID: CHEMBL2071 Sources: http://www.drugbank.ca/drugs/DB00222	Agonist 2678	3.0 nM [IC50]
Potassium channel, inwardly rectifying, subfamily J, member 11 1 Target ID: CHEMBL1886 Sources: http://www.drugbank.ca/drugs/DB00222	Inhibitor 8297	400.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Type 2 diabetes mellitus 259 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020496s021lbl.pdf	Primary		Approved 8429	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
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
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

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
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
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

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 1037		inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
UGT1A1 204 UGT1A3 84 UGT1A6 108 UGT1A9 116 UGT2B7 146 UGT2B15 64	OATP1B1 406

Drug as perpetrator

Target	Modality	Activity
UGT1A1 254	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22957438/	yes [Inhibition 100 uM]
UGT1A3 93	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22957438/	yes [Inhibition 100 uM]
UGT1A6 141	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22957438/	yes [Inhibition 100 uM]
UGT1A9 121	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22957438/	yes [Inhibition 100 uM]
UGT2B15 64	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22957438/	yes [Inhibition 100 uM]
UGT2B7 157	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22957438/	yes [Inhibition 100 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
OATP1B1 406	substrate 3367 Sources: https://www.nature.com/articles/s41598-018-29351-4	yes
CYP2C9 1037	substrate 3367 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 1647	inhibitor 1626 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
Effectiveness of nateglinide on in vitro insulin secretion from rat pancreatic islets desensitized to sulfonylureas.	2001	12369729
Oral hypoglycemic agents: insulin secretagogues, alpha-glucosidase inhibitors and insulin sensitizers.	2001	11460577
Comparison of the effects of three sulfonylureas on in vivo insulin action.	2001	11455676
Clinical review of glimepiride.	2001 Apr	11336617
Insulin-mimetic signaling by the sulfonylurea glimepiride and phosphoinositolglycans involves distinct mechanisms for redistribution of lipid raft components.	2001 Dec 4	11724574
[Glimepiride (Amaryl): a review of its pharmacological and clinical profile].	2001 Jul	11496829
Glimepiride, a novel sulfonylurea, does not abolish myocardial protection afforded by either ischemic preconditioning or diazoxide.	2001 Jun 26	11425777
Effects of sulfonylurea derivatives on ischemia-induced loss of function in the isolated rat heart.	2001 May 4	11348634
Predictors of response to glimepiride in patients with type 2 diabetes mellitus.	2001 Nov	11694855
Improved glycaemic control by addition of glimepiride to metformin monotherapy in type 2 diabetic patients.	2001 Oct	11678974
[Progress in studies on antidiabetic agents].	2001 Sep	12580115
Haemodynamic and metabolic effects of low daily dose sulphonylureas in diabetic dog hearts.	2002	12189779
[Differential type 2 diabetes therapy based on pathophysiological aspects].	2002 Aug	12235731
[Molecular mechanisms of insulin secretion].	2002 Dec	12703060
Vascular effects of glibenclamide vs. glimepiride and metformin in Type 2 diabetic patients.	2002 Feb	11874430
Antiaggregatory activity of hypoglycaemic sulphonylureas.	2002 Jul	12136403
Rosiglitazone in combination with glimepiride plus metformin in type 2 diabetic patients.	2002 Jul	12087036
Glimepiride--well tolerated in daily practice.	2002 Jul-Aug	12402929
Screening, library-assisted identification and validated quantification of oral antidiabetics of the sulfonylurea-type in plasma by atmospheric pressure chemical ionization liquid chromatography-mass spectrometry.	2002 Jun 15	12015271
Participation of high glucose concentrations in neutrophil adhesion and surface expression of adhesion molecules on cultured human endothelial cells: effect of antidiabetic medicines.	2002 May-Jun	12015189
Acute effect of glimepiride on insulin-stimulated glucose metabolism in glucose-tolerant insulin-resistant offspring of patients with type 2 diabetes.	2002 Nov	12401758
[Combination therapy with insulin and sulfonylurea].	2002 Sep	12387031
Glyburide and glimepiride pharmacokinetics in subjects with different CYP2C9 genotypes.	2002 Sep	12235454
Glimepiride improves both first and second phases of insulin secretion in type 2 diabetes.	2002 Sep	12196435
[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
[Sulfonylurea receptors and their interaction with glimepiride].	2003	12774471
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 Aug	14768770
Hormonal counterregulation and consecutive glimepiride serum concentrations during severe hypoglycaemia associated with glimepiride therapy.	2003 Dec	14634699
Glimepiride and serum adiponectin level in type 2 diabetic subjects: response to Nagasaka et al.	2003 Dec	14633838
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 Feb	12749508
Differential effects of sulphonylureas on the vasodilatory response evoked by K(ATP) channel openers.	2003 Feb	12588631
Impairment of myocardial protection in type 2 diabetic patients.	2003 Feb	12574175
Efficacy and safety profile of glimepiride in Mexican American Patients with type 2 diabetes mellitus: a randomized, placebo-controlled study.	2003 Jan	12637120
Effects of glimepiride on HbA(1c) and body weight in Type 2 diabetes: results of a 1.5-year follow-up study.	2003 Jul	12849919
Glimepiride reduces mononuclear activation of the redox-sensitive transcription factor nuclear factor-kappa B.	2003 Jul	12795658
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 Jun	12814458
Characteristics and time course of severe glimepiride- versus glibenclamide-induced hypoglycaemia.	2003 Jun	12698302
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 Jun 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 Jun 17	12809451
Glimepiride in type 2 diabetes mellitus: a review of the worldwide therapeutic experience.	2003 Mar	12852703
The mechanisms underlying the unique pharmacodynamics of nateglinide.	2003 Mar	12652357
Study of glimepiride-b-cyclodextrin complex.	2003 Nov	14971307
Efficacy of sulfonylureas with insulin in type 2 diabetes mellitus.	2003 Nov	14565810
Design of the cooperative study on glycemic control and complications in diabetes mellitus type 2: Veterans Affairs Diabetes Trial.	2003 Nov-Dec	14583175
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 Jan	14704628
Determination of glimepiride in human plasma by liquid chromatography-electrospray ionization tandem mass spectrometry.	2004 Jan 5	14659441
Prevention of weight gain in type 2 diabetes requiring insulin treatment.	2004 Mar	14746576

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)

Name

Type

Language

GLIMEPIRIDE

Official 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

DUETACT COMPONENT GLIMEPIRIDE

Common Name

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 COMPONENT OF DUETACT

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