ESZOPICLONE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C17H17ClN6O3
Molecular Weight	388.808
Optical Activity	( + )
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CN1CCN(CC1)C(=O)O[C@@H]2N(C(=O)C3=C2N=CC=N3)C4=CC=C(Cl)C=N4

InChI

InChIKey=GBBSUAFBMRNDJC-INIZCTEOSA-N

InChI=1S/C17H17ClN6O3/c1-22-6-8-23(9-7-22)17(26)27-16-14-13(19-4-5-20-14)15(25)24(16)12-3-2-11(18)10-21-12/h2-5,10,16H,6-9H2,1H3/t16-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C17H17ClN6O3
Molecular Weight	388.808
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

Eszopiclone is a nonbenzodiazepine hypnotic, pyrrolopyrazine derivative of the cyclopyrrolone class and is indicated for the short-term treatment of insomnia. While Eszopiclone is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties, it interacts with the gamma-aminobutyric acid-benzodiazepine (GABABZ) receptor complex. Subunit modulation of the GABABZ receptor chloride channel macromolecular complex is hypothesized to be responsible for some of the pharmacological properties of benzodiazepines, which include sedative, anxiolytic, muscle relaxant, and anticonvulsive effects in animal models. Eszopiclone binds selectively to the brain alpha subunit of the GABA A omega-1 receptor. The mechanism of action of Eszopiclone is not completely understood. It is thought that Eszopiclone acts on the benzodiazepine receptors as an agonist and interacts with GABA-receptor complexes. Used for the treatment of insomnia.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
GABA-A receptor; anion channel 203	Agonist 2,752
GABA receptor alpha-1 subunit 19	Agonist 2,752	50.1 nM [Ki]
GABA receptor alpha-2 subunit 7	Agonist 2,752	114.0 nM [Ki]
GABA receptor alpha-4 subunit 2	Agonist 2,752	102.0 nM [Ki]
GABA receptor alpha-3 subunit 6	Agonist 2,752	162.0 nM [Ki]
Translocator protein 12	Agonist 2,752

Conditions

Condition	Modality	Targets	Highest Phase	Product
Insomnia 111	Primary		Approved 8,583	LUNESTA

C_max

Value	Dose	Analyte	Population
6.15 ng/mL	1 mg single, oral	ESZOPICLONE plasma	Homo sapiens
19.88 ng/mL	3 mg single, oral	ESZOPICLONE plasma	Homo sapiens
40.28 ng/mL	6 mg single, oral	ESZOPICLONE plasma	Homo sapiens
10.29 ng/mL	1 mg single, oral	ESZOPICLONE plasma	Homo sapiens
25.48 ng/mL	3 mg single, oral	ESZOPICLONE plasma	Homo sapiens
54.68 ng/mL	6 mg single, oral	ESZOPICLONE plasma	Homo sapiens
9.58 ng/mL	1 mg 1 times / day multiple, oral	ESZOPICLONE plasma	Homo sapiens
26.18 ng/mL	3 mg 1 times / day multiple, oral	ESZOPICLONE plasma	Homo sapiens
59.63 ng/mL	6 mg 1 times / day multiple, oral	ESZOPICLONE plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
54.76 ng × h/mL	1 mg single, oral	ESZOPICLONE plasma	Homo sapiens
166.21 ng × h/mL	3 mg single, oral	ESZOPICLONE plasma	Homo sapiens
338.26 ng × h/mL	6 mg single, oral	ESZOPICLONE plasma	Homo sapiens
62.96 ng × h/mL	1 mg single, oral	ESZOPICLONE plasma	Homo sapiens
187.76 ng × h/mL	3 mg single, oral	ESZOPICLONE plasma	Homo sapiens
379.04 ng × h/mL	6 mg single, oral	ESZOPICLONE plasma	Homo sapiens
66.05 ng × h/mL	1 mg 1 times / day multiple, oral	ESZOPICLONE plasma	Homo sapiens
191.07 ng × h/mL	3 mg 1 times / day multiple, oral	ESZOPICLONE plasma	Homo sapiens
409.31 ng × h/mL	6 mg 1 times / day multiple, oral	ESZOPICLONE plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
6.7 h	2 mg single, oral		ESZOPICLONE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
44.45%			ESZOPICLONE plasma	Homo sapiens

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,946 inhibitor 2,252 inducer 1,087	inhibitor 2,438 inducer 440	inhibitor 2,507 inducer 109

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2,153 CYP2A6 879 CYP2C19 2,057 CYP2E1 1,060	CYP2E1 729	CYP1A2 832 CYP2A6 86 CYP2C19 329 CYP2E1 131

Drug as perpetrator

Show entries

Target	Modality	Activity
CYP1A2 2,333	inducer 1,966	no
CYP1A2 2,333	inhibitor 4,027	no
CYP2A6 911	inducer 1,966	no
CYP2A6 911	inhibitor 4,027	no
CYP2C19 2,141	inducer 1,966	no

Showing 1 to 5 of 14 entries

Previous1 2 3Next

Drug as victim

Show entries

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2E1 729	substrate 4,014	likely
CYP3A4 1,946	substrate 4,014	yes		yes (co-administration study)

Showing 1 to 2 of 2 entries

Previous1Next

Sourcing

Sourcing

Show entries

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:53760	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:53760
ChemicalBook	CB1468825	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1468825
eMolecules	2728749	https://www.emolecules.com/cgi-bin/more?vid=2728749
ZINC	ZINC000019632834	http://zinc15.docking.org/substances/ZINC000019632834

Showing 1 to 4 of 4 entries

Previous1Next

PubMed

Show entries

Title	Date	PubMed
Evaluation of eszopiclone discontinuation after cotherapy with fluoxetine for insomnia with coexisting depression.	2007 Feb 15	17557453

Showing 1 to 1 of 1 entries

Previous1Next

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Insomnia Initial dose: 1 mg orally immediately before bedtime Maintenance dose: 1 to 3 mg orally immediately before bedtime Maximum dose: 3 mg orally immediately before bedtime

Route of Administration: Oral

In Vitro Use Guide

10 uM Eszopiclone increased the mean amplitude of the IGV-induced outward current from 19.7 ± 3.9 pA to 47.1 ± 7.8 pA (n = 10) and increased duration from 396.5 ± 24.0 s to 568.8 ± 40.5 s in rat pedunculopontine neurons.