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

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 of GLIMEPIRIDE

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
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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
74.05 μg/L
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
646.98 μg × h/L
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
4.08 h
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
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.5%
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

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer







Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [Inhibition 100 uM]
yes [Inhibition 100 uM]
yes [Inhibition 100 uM]
yes [Inhibition 100 uM]
yes [Inhibition 100 uM]
yes [Inhibition 100 uM]
Drug as victim

Drug as victim

Tox targets
PubMed

PubMed

TitleDatePubMed
[Acute cholestatic hepatitis induced by glimepiride].
2000 Dec
Effectiveness of nateglinide on in vitro insulin secretion from rat pancreatic islets desensitized to sulfonylureas.
2001
Glucose-dependent and glucose-sensitizing insulinotropic effect of nateglinide: comparison to sulfonylureas and repaglinide.
2001
Oral hypoglycemic agents: insulin secretagogues, alpha-glucosidase inhibitors and insulin sensitizers.
2001
Management of type 2 diabetes mellitus in the elderly: special considerations.
2001
Clinical review of glimepiride.
2001 Apr
Sulfonylurea treatment of type 2 diabetic patients does not reduce the vasodilator response to ischemia.
2001 Apr
Effects of fluconazole and fluvoxamine on the pharmacokinetics and pharmacodynamics of glimepiride.
2001 Apr
The NEPI antidiabetes study (NANSY). 1: short-term dose-effect relations of glimepiride in subjects with impaired fasting glucose.
2001 Dec
Analysis of glimepiride by using derivative UV spectrophotometric method.
2001 Jan
[Glimepiride (Amaryl): a review of its pharmacological and clinical profile].
2001 Jul
Glimepiride, a novel sulfonylurea, does not abolish myocardial protection afforded by either ischemic preconditioning or diazoxide.
2001 Jun 26
Glimepiride block of cloned beta-cell, cardiac and smooth muscle K(ATP) channels.
2001 May
Effects of sulfonylurea derivatives on ischemia-induced loss of function in the isolated rat heart.
2001 May 4
Effect of gemfibrozil on the pharmacokinetics and pharmacodynamics of glimepiride.
2001 Nov
Predictors of response to glimepiride in patients with type 2 diabetes mellitus.
2001 Nov
Amaryl (glimepiride) in patients with type 2 diabetes mellitus.
2002
Influence of diabetic state and that of different sulfonylureas on the size of myocardial infarction with and without ischemic preconditioning in rabbits.
2002 Aug
Sulfonylurea stimulation of insulin secretion.
2002 Dec
Efficacy of glimepiride for the treatment of diabetes occurring during glucocorticoid therapy.
2002 Dec
Effect of glimepiride on insulin-stimulated glycogen synthesis in cultured human skeletal muscle cells: a comparison to glibenclamide.
2002 Dec
[Fear of the injection must not be an argument. Every second type 2 diabetic patient needs insulin].
2002 Dec 5
Vascular effects of glibenclamide vs. glimepiride and metformin in Type 2 diabetic patients.
2002 Feb
Antiaggregatory activity of hypoglycaemic sulphonylureas.
2002 Jul
Glimepiride--well tolerated in daily practice.
2002 Jul-Aug
Oral hypoglycemic sulfonylurea glimepiride preserves the myoprotective effects of ischemic preconditioning.
2002 Jun 15
Cholesterol depletion blocks redistribution of lipid raft components and insulin-mimetic signaling by glimepiride and phosphoinositolglycans in rat adipocytes.
2002 Mar
Interaction of nateglinide with K(ATP) channel in beta-cells underlies its unique insulinotropic action.
2002 May 3
Acute effect of glimepiride on insulin-stimulated glucose metabolism in glucose-tolerant insulin-resistant offspring of patients with type 2 diabetes.
2002 Nov
Dynamics of plasma membrane microdomains and cross-talk to the insulin signalling cascade.
2002 Oct 30
[Combination therapy with insulin and sulfonylurea].
2002 Sep
[Glimepiride].
2002 Sep
Glyburide and glimepiride pharmacokinetics in subjects with different CYP2C9 genotypes.
2002 Sep
[Glimepiride--an oral antidiabetic agent].
2003
Glimepiride treatment and IGF-I in adolescents with type 1 diabetes: a prospective, randomized, double-blind, placebo-controlled study.
2003 Apr
Differential effects of sulphonylureas on the vasodilatory response evoked by K(ATP) channel openers.
2003 Feb
Efficacy and safety profile of glimepiride in Mexican American Patients with type 2 diabetes mellitus: a randomized, placebo-controlled study.
2003 Jan
Lispro insulin and metformin versus other combination in the diabetes mellitus type 2 management after secondary oral antidiabetic drug failure.
2003 Jun
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
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
Glimepiride in type 2 diabetes mellitus: a review of the worldwide therapeutic experience.
2003 Mar
The mechanisms underlying the unique pharmacodynamics of nateglinide.
2003 Mar
[Differences between oral antidiabetics].
2003 Mar 20
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 Mar-Apr
Differential selectivity of insulin secretagogues: mechanisms, clinical implications, and drug interactions.
2003 Mar-Apr
Effects of sulfonylureas on K(ATP) channel-dependent vasodilation.
2003 Mar-Apr
Efficacy of sulfonylureas with insulin in type 2 diabetes mellitus.
2003 Nov
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 Jan
Comparison of the effects of glimepiride and glibenclamide on adipose tissue tumour necrosis factor-alpha mRNA expression and cellularity.
2004 Jan
Long-acting sulfonylureas -- long-acting hypoglycaemia.
2004 Jan 19
Patents

Sample Use Guides

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
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 Fri Dec 15 15:51:28 GMT 2023
Edited
by admin
on Fri Dec 15 15:51:28 GMT 2023
Record UNII
6KY687524K
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
GLIMEPIRIDE
EMA EPAR   EP   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN   INN  
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
Created by admin on Fri Dec 15 15:51:28 GMT 2023 , Edited by admin on Fri Dec 15 15:51:28 GMT 2023
LIVERTOX 459
Created by admin on Fri Dec 15 15:51:28 GMT 2023 , Edited by admin on Fri Dec 15 15:51:28 GMT 2023
NDF-RT N0000008054
Created by admin on Fri Dec 15 15:51:28 GMT 2023 , Edited by admin on Fri Dec 15 15:51:28 GMT 2023
WHO-VATC QA10BD06
Created by admin on Fri Dec 15 15:51:28 GMT 2023 , Edited by admin on Fri Dec 15 15:51:28 GMT 2023
NDF-RT N0000008054
Created by admin on Fri Dec 15 15:51:28 GMT 2023 , Edited by admin on Fri Dec 15 15:51:28 GMT 2023
WHO-VATC QA10BB12
Created by admin on Fri Dec 15 15:51:28 GMT 2023 , Edited by admin on Fri Dec 15 15:51:28 GMT 2023
NCI_THESAURUS C97936
Created by admin on Fri Dec 15 15:51:28 GMT 2023 , Edited by admin on Fri Dec 15 15:51:28 GMT 2023
WHO-ATC A10BB12
Created by admin on Fri Dec 15 15:51:28 GMT 2023 , Edited by admin on Fri Dec 15 15:51:28 GMT 2023
WHO-ATC A10BD06
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WHO-ATC A10BD04
Created by admin on Fri Dec 15 15:51:28 GMT 2023 , Edited by admin on Fri Dec 15 15:51:28 GMT 2023
NDF-RT N0000175608
Created by admin on Fri Dec 15 15:51:28 GMT 2023 , Edited by admin on Fri Dec 15 15:51:28 GMT 2023
WHO-VATC QA10BD04
Created by admin on Fri Dec 15 15:51:28 GMT 2023 , Edited by admin on Fri Dec 15 15:51:28 GMT 2023
Code System Code Type Description
ChEMBL
CHEMBL1481
Created by admin on Fri Dec 15 15:51:28 GMT 2023 , Edited by admin on Fri Dec 15 15:51:28 GMT 2023
PRIMARY
NCI_THESAURUS
C29073
Created by admin on Fri Dec 15 15:51:28 GMT 2023 , Edited by admin on Fri Dec 15 15:51:28 GMT 2023
PRIMARY
RXCUI
25789
Created by admin on Fri Dec 15 15:51:28 GMT 2023 , Edited by admin on Fri Dec 15 15:51:28 GMT 2023
PRIMARY RxNorm
WIKIPEDIA
GLIMEPIRIDE
Created by admin on Fri Dec 15 15:51:28 GMT 2023 , Edited by admin on Fri Dec 15 15:51:28 GMT 2023
PRIMARY
RS_ITEM_NUM
1292303
Created by admin on Fri Dec 15 15:51:28 GMT 2023 , Edited by admin on Fri Dec 15 15:51:28 GMT 2023
PRIMARY
MERCK INDEX
m5745
Created by admin on Fri Dec 15 15:51:28 GMT 2023 , Edited by admin on Fri Dec 15 15:51:28 GMT 2023
PRIMARY Merck Index
CAS
93479-97-1
Created by admin on Fri Dec 15 15:51:28 GMT 2023 , Edited by admin on Fri Dec 15 15:51:28 GMT 2023
PRIMARY
LACTMED
Glimepiride
Created by admin on Fri Dec 15 15:51:28 GMT 2023 , Edited by admin on Fri Dec 15 15:51:28 GMT 2023
PRIMARY
FDA UNII
6KY687524K
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PRIMARY
CHEBI
5383
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PRIMARY
SMS_ID
100000085456
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PRIMARY
EVMPD
SUB07925MIG
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PRIMARY
INN
5718
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PRIMARY
DRUG BANK
DB00222
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PRIMARY
NSC
759809
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PRIMARY
IUPHAR
6820
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PRIMARY
DAILYMED
6KY687524K
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PRIMARY
MESH
C057619
Created by admin on Fri Dec 15 15:51:28 GMT 2023 , Edited by admin on Fri Dec 15 15:51:28 GMT 2023
PRIMARY
EPA CompTox
DTXSID5040675
Created by admin on Fri Dec 15 15:51:28 GMT 2023 , Edited by admin on Fri Dec 15 15:51:28 GMT 2023
PRIMARY
USAN
EE-37
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PRIMARY
DRUG CENTRAL
1300
Created by admin on Fri Dec 15 15:51:28 GMT 2023 , Edited by admin on Fri Dec 15 15:51:28 GMT 2023
PRIMARY
Related Record Type Details
BASIS OF STRENGTH->SUBSTANCE
ASSAY (HPLC)
USP
TRANSPORTER -> SUBSTRATE
Clearance of glimepiridein OATP1B1*5 and *15 was significantly reduced compared to the wild-type.
METABOLIC ENZYME -> SUBSTRATE
Clearance of glimepiride CYP2C9*2 and *3 was significantly reduced compared to the wild-type.
BINDER->LIGAND
BINDING
TARGET -> INHIBITOR
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EP
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Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC