Identification

Summary

Eszopiclone is a sedative-hypnotic used in the treatment of insomnia, improving both the latency phase and the maintenance phase of sleep.

Brand Names
Lunesta
Generic Name
Eszopiclone
DrugBank Accession Number
DB00402
Background

Eszopiclone, marketed by Sepracor under the brand-name Lunesta, is a nonbenzodiazepine hypnotic drug used to treat insomnia. It is the active stereoisomer of zopiclone, belonging to the class of drugs known as cyclopyrrolones.1,12 Cyclopyrrolone drugs demonstrate high efficacy and low toxicity9, offering a safer alternative to other drugs used for insomnia.

One major benefit of eszopiclone is that it is approved by the FDA for the long-term treatment of insomnia. This sets it apart from many other hypnotic sedatives, which are generally approved only for the relief of short-term (6-8 weeks) insomnia. Eszopiclone was initially approved by the FDA in 2004.10

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 388.808
Monoisotopic: 388.105066147
Chemical Formula
C17H17ClN6O3
Synonyms
  • (+)-(5S)-6-(5-Chloropyridin-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo(3,4-b)pyrazin-5-yl 4-methylpiperazine-1-carboxylate
  • (+)-(5S)-6-(5-chloropyridin-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-yl-4-methylpiperazine-1-carboxylate
  • (+)-Zopiclone
  • (S)-6-(5-Chloro-2-pyridinyl)- 7-oxo- 6,7-dihydro- 5H-pyrrolo[3,4-b]pyrazin-5-yl- 4-methyl- 1-piperazinecarboxylate
  • (S)-Zopiclone
  • 1-Piperazinecarobxylic acid,4-methyl-,(5S)-6-(5-chloro-2-pyridinyl)-6,7-dihydro-7-oxo-5H-pyrrolo[3,4-b]pyrazin-5-yl ester
  • Esopiclone
  • Eszopiclone
External IDs
  • GSK-1755165

Pharmacology

Indication

Eszopiclone is indicated for the treatment of insomnia.10

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Eszopiclone rapidly induces sleep and decreases sleep latency. It also aids in the maintenance of sleep, preventing frequent awakenings.3,4,10 This drug has shown anticonvulsant and muscle relaxant properties in animals but is used in humans for its sedating effects.9

Eszopiclone is a central nervous system depressant with various effects. These include changes in alertness and motor coordination and the risk of next morning impairment, increasing with the amount of eszopiclone administered. Exercise caution and advise against driving a motor vehicle or activities that require full mental alertness the next morning.10 Complex sleep behaviors may result from eszopiclone use. Eszopiclone should be discontinued in these cases.15 Avoid the use of alcohol and other CNS depressants when eszopiclone is administered. Advise patients to skip the eszopiclone dose if alcohol has been consumed before bed or during the evening. Use the smallest dose of eszopiclone as possible, especially in elderly patients, who may experience exaggerated drug effects. Though the potential for dependence and abuse with eszopiclone is lower than for other hypnotic drugs, this drug has been abused and is known to cause dependence.14

Mechanism of action

The exact mechanism of action of eszopiclone is unknown at this time but is thought to occur via binding with the GABA receptor complexes at binding sites located near benzodiazepine receptors, possibly explaining its hypnotic and sedative effects.3,10 It has particular affinity for GABA-A (or GABAA) receptor subunits 1, 3 and 5.5,6,7 Eszopiclone increases GABA-A channel currents significantly.5 GABA-A channels are major inhibitory channels that cause CNS depression when their receptors are activated.8

TargetActionsOrganism
AGamma-aminobutyric acid receptor subunit alpha-1
potentiator
Humans
UGamma-aminobutyric acid receptor subunit alpha-2
agonist
Humans
AGABA(A) Receptor
positive allosteric modulator
Humans
UGamma-aminobutyric acid receptor subunit alpha-3
agonist
Humans
UGamma-aminobutyric acid receptor subunit alpha-5
agonist
Humans
Absorption

Eszopiclone is rapidly absorbed and the peak concentration is reached within about 1 hour after oral administration.3,10 The mean AUC after a 3 mg dose of eszopiclone was 278 ng/mL × h.1 The consumption of a high-fat has been shown to slow absorption. Steady-state concentrations of eszopiclone are reached within 24-48 hours.4

Volume of distribution

The volume of distribution of eszopiclone is estimated at 89.9L11

Protein binding

This drug is 52-59% bound to plasma proteins.10

Metabolism

Following oral administration, eszopiclone is extensively biotransformed and the major metabolites are S-desmethylzopiclone and zopiclone-N-oxide, which are largely inactive.2. The enzymes involved in the metabolism of eszopiclone are CYP3A (the primary metabolizing enzyme), CYP2C8, and CYP2E1.2 The N-oxide derivative shows weak pharmacological activity in animals. The N-desmethyl metabolite is pharmacologically active.10

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Route of elimination

Only about 10% of an eszopiclone dose is found excreted in the urine as the parent drug.3,10 As much as 75% of an orally administered dose of racemic zopiclone as is found to be excreted in the urine in the form of metabolites. Eszopiclone, the S-isomer of racemic zopiclone, would likely show the same excretion pattern.10

Half-life

The half-life is 6.1 hours in healthy patients but is prolonged in various patients, including those with hepatic impairment, elderly patients, in addition to those taking CYP3A enzyme inhibiting drugs.1,10

Clearance

The mean clearance of eszopiclone in young, healthy volunteers was 184 mL/min in one pharmacokinetic study.1

Adverse Effects
Adverseeffects
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Toxicity

The oral LD50 of eszopiclone in rats is 980 mg/kg and 3200 mg/kg in rabbits.13 Symptoms of overdose may include mental status changes and somnolence, demonstrating general exaggeration of the drug's pharmacological effects. Perform gastric lavage and offer supportive treatment if an overdose is suspected, including intravenous fluids as required. Flumazenil may be used. Vital signs should be closely monitored in addition to patient symptoms. Appropriate medical interventions should be employed. The possibility of an overdose with multiple drugs should be considered. Ensure to contact the local poison control center for the most updated management of hypnotic drug overdose.10

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe risk or severity of CNS depression can be increased when 1,2-Benzodiazepine is combined with Eszopiclone.
AbacavirEszopiclone may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbametapirThe serum concentration of Eszopiclone can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Eszopiclone can be increased when combined with Abatacept.
AbirateroneThe metabolism of Eszopiclone can be decreased when combined with Abiraterone.
AcalabrutinibThe metabolism of Eszopiclone can be decreased when combined with Acalabrutinib.
AceclofenacAceclofenac may decrease the excretion rate of Eszopiclone which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Eszopiclone which could result in a higher serum level.
AcetaminophenThe serum concentration of Eszopiclone can be decreased when it is combined with Acetaminophen.
AcetazolamideThe risk or severity of CNS depression can be increased when Acetazolamide is combined with Eszopiclone.
Interactions
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Food Interactions
  • Avoid alcohol.
  • Do not take with or immediately after a high-fat meal. This decreases the absorption of eszopiclone.

Products

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Product Images
International/Other Brands
Dorplen (LKM) / Esleep (Opsonin) / Eszop (Silesia) / Fulnite (Sun) / Inductal (Roemmers) / Isoklon (Tecnoquimicas) / Nirvan (Saval) / Noptic (Andromaco) / Plessir (Medipharm) / Sanilent (Sanitas) / Sleepil (Aristopharma) / Sono (Acme) / Valnoc (Drugtech) / Wen Fei (Tasly) / Zopilone (Incepta) / Zopinon (Chile)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
LunestaTablet, coated3 mg/1OralPhysicians Total Care, Inc.2005-08-24Not applicableUS flag63402 0193 10 nlmimage10 f73cfb97
LunestaTablet, coated3 mg/1OralA-S Medication Solutions2005-04-042016-10-31US flag50090 092420180907 15195 wn8ujg
LunestaTablet, coated1 mg/1OralSunovion Pharmaceuticals Inc.2005-04-04Not applicableUS flag
LunestaTablet, coated3 mg/1OralCaremark L.L.C.2009-01-012012-07-31US flag
LunestaTablet, coated3 mg/1OralLake Erie Medical DBA Quality Care Products LLC2011-07-182014-06-01US flag
LunestaTablet, coated3 mg/1Oralbryant ranch prepack2005-04-04Not applicableUS flag63629 314220180907 15195 1hmvbwi
LunestaTablet, coated3 mg/1OralH.J. Harkins Company2005-04-04Not applicableUS flag52959 085220210411 23328 e1se9h
LunestaTablet3 mgOralSunovion2020-10-20Not applicableCanada flag
LunestaTablet, coated2 mg/1OralSt. Marys Medical Park Pharmacy2005-04-042013-01-31US flag
LunestaTablet, coated2 mg/1OralRebel Distributors2009-01-01Not applicableUS flag21695 022520210315 21055 iw4tpi
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
EszopicloneTablet, film coated1 mg/1OralMacleods Pharmaceuticals Limited2015-01-31Not applicableUS flag
EszopicloneTablet1 mg/1OralLake Erie Medical DBA Quality Care Products LLC2014-04-152019-10-11US flag
EszopicloneTablet, film coated1 mg/1OralPreferred Pharmaceuticals, Inc.2015-04-152019-09-10US flag
EszopicloneTablet, film coated1 mg/1OralUnit Dose Services2014-04-15Not applicableUS flag
EszopicloneTablet, film coated2 mg/1OralDirect Rx2017-02-13Not applicableUS flag
EszopicloneTablet, film coated1 mg/1OralAidarex Pharmaceuticals LLC2014-04-15Not applicableUS flag
EszopicloneTablet, film coated2 mg/1OralGolden State Medical Supply, Inc.2013-03-26Not applicableUS flag
EszopicloneTablet, coated3 mg/1OralDr. Reddy's Laboratories Limited2014-04-15Not applicableUS flag
EszopicloneTablet2 mg/1OralProficient Rx LP2014-04-15Not applicableUS flag
EszopicloneTablet, coated3 mg/1OralREMEDYREPACK INC.2017-11-022020-05-06US flag

Categories

ATC Codes
N05CF04 — Eszopiclone
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as cyclopyrrolones. These are compounds belonging to a family of pyridin-2-ylpyrrole based chemicals. The pyrrole is usually fused to a benzene, pyrimidine, or dithiin.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyrrolopyrazines
Sub Class
Cyclopyrrolones
Direct Parent
Cyclopyrrolones
Alternative Parents
Piperazine carboxylic acids / 2-heteroaryl carboxamides / N-methylpiperazines / Pyridines and derivatives / Pyrazines / Aryl chlorides / Imidolactams / Tertiary carboxylic acid amides / Carbamate esters / Heteroaromatic compounds
show 9 more
Substituents
1,4-diazinane / 2-heteroaryl carboxamide / Amine / Amino acid or derivatives / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Carbamic acid ester / Carbonic acid derivative
show 25 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
zopiclone (CHEBI:53760)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
UZX80K71OE
CAS number
138729-47-2
InChI Key
GBBSUAFBMRNDJC-INIZCTEOSA-N
InChI
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
IUPAC Name
(5S)-6-(5-chloropyridin-2-yl)-7-oxo-5H,6H,7H-pyrrolo[3,4-b]pyrazin-5-yl 4-methylpiperazine-1-carboxylate
SMILES
CN1CCN(CC1)C(=O)O[C@@H]1N(C(=O)C2=NC=CN=C12)C1=NC=C(Cl)C=C1

References

Synthesis Reference

Marioara MENDELOVICI, Anita LIBERMAN, Alex MAINFELD, Nina FINKELSTEIN, "METHODS FOR PREPARING ESZOPICLONE CRYSTALLINE FORM A, SUBSTANTIALLY PURE ESZOPICLONE AND OPTICALLY ENRICHED ESZOPICLONE." U.S. Patent US20070270590, issued November 22, 2007.

US20070270590
General References
  1. Greenblatt DJ, Zammit GK: Pharmacokinetic evaluation of eszopiclone: clinical and therapeutic implications. Expert Opin Drug Metab Toxicol. 2012 Dec;8(12):1609-18. doi: 10.1517/17425255.2012.741588. Epub 2012 Nov 6. [Article]
  2. Carlson JN, Haskew R, Wacker J, Maisonneuve IM, Glick SD, Jerussi TP: Sedative and anxiolytic effects of zopiclone's enantiomers and metabolite. Eur J Pharmacol. 2001 Mar;415(2-3):181-9. doi: 10.1016/s0014-2999(01)00851-2. [Article]
  3. Brielmaier BD: Eszopiclone (Lunesta): a new nonbenzodiazepine hypnotic agent. Proc (Bayl Univ Med Cent). 2006 Jan;19(1):54-9. doi: 10.1080/08998280.2006.11928127. [Article]
  4. Halas CJ: Eszopiclone. Am J Health Syst Pharm. 2006 Jan 1;63(1):41-8. doi: 10.2146/ajhp050357. [Article]
  5. Dixon CL, Harrison NL, Lynch JW, Keramidas A: Zolpidem and eszopiclone prime alpha1beta2gamma2 GABAA receptors for longer duration of activity. Br J Pharmacol. 2015 Jul;172(14):3522-36. doi: 10.1111/bph.13142. Epub 2015 May 11. [Article]
  6. Nutt DJ, Stahl SM: Searching for perfect sleep: the continuing evolution of GABAA receptor modulators as hypnotics. J Psychopharmacol. 2010 Nov;24(11):1601-12. doi: 10.1177/0269881109106927. Epub 2009 Nov 26. [Article]
  7. Hanson SM, Morlock EV, Satyshur KA, Czajkowski C: Structural requirements for eszopiclone and zolpidem binding to the gamma-aminobutyric acid type-A (GABAA) receptor are different. J Med Chem. 2008 Nov 27;51(22):7243-52. doi: 10.1021/jm800889m. [Article]
  8. Goetz T, Arslan A, Wisden W, Wulff P: GABA(A) receptors: structure and function in the basal ganglia. Prog Brain Res. 2007;160:21-41. doi: 10.1016/S0079-6123(06)60003-4. [Article]
  9. Goa KL, Heel RC: Zopiclone. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy as an hypnotic. Drugs. 1986 Jul;32(1):48-65. doi: 10.2165/00003495-198632010-00003. [Article]
  10. FDA Approved Drug Products: Lunesta (eszopiclone) oral tablets [Link]
  11. FDA review, Eszopiclone [Link]
  12. Pubchem, Eszopiclone [Link]
  13. MSDS, Eszopiclone [Link]
  14. Lunesta label 2019 [Link]
  15. FDA news [Link]
Human Metabolome Database
HMDB0014546
PubChem Compound
969472
PubChem Substance
46505809
ChemSpider
839530
BindingDB
26265
RxNav
461016
ChEBI
53760
ChEMBL
CHEMBL1522
ZINC
ZINC000019632834
Therapeutic Targets Database
DAP000933
PharmGKB
PA162630444
RxList
RxList Drug Page
Wikipedia
Eszopiclone

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedNot AvailableInsomnia / Migraine1
4CompletedBasic ScienceInsomnia1
4CompletedDiagnosticObstructive Sleep Apnea (OSA)1
4CompletedSupportive CareAcute Coronary Syndrome (ACS) / Sleep disorders and disturbances1
4CompletedSupportive CareObstructive Sleep Apnea (OSA)1
4CompletedTreatmentAnxiety / Depression / Insomnia1
4CompletedTreatmentDepression / Sleep Initiation and Maintenance Disorders1
4CompletedTreatmentFibromyalgia (FM) / Insomnia1
4CompletedTreatmentGeneralized Anxiety Disorder / Insomnia1
4CompletedTreatmentInsomnia2

Pharmacoeconomics

Manufacturers
  • Sepracor inc
  • Sepracor Inc.
Packagers
  • A-S Medication Solutions LLC
  • Caremark LLC
  • Centaur Pharmaceuticals Pvt Ltd.
  • DispenseXpress Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • H.J. Harkins Co. Inc.
  • Innoviant Pharmacy Inc.
  • Lake Erie Medical and Surgical Supply
  • Lupin Pharmaceuticals Inc.
  • Mckesson Corp.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • Patheon Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Rebel Distributors Corp.
  • Sepracor Pharmaceuticals Inc.
  • Southwood Pharmaceuticals
  • Stat Rx Usa
Dosage Forms
FormRouteStrength
Tablet, film coatedOral2 mg
Tablet, coatedOral3 mg
Tablet, film coatedOral
TabletOral1 mg/1
TabletOral2 mg/1
TabletOral3 mg/1
Tablet, film coatedOral1 mg/1
Tablet, film coatedOral2 mg/1
Tablet, film coatedOral3 mg/1
Tablet, film coatedOropharyngeal3 mg/1
Tablet, coatedOral1 mg
Tablet, film coatedOral1 mg
TabletOral1 mg
TabletOral2 mg
TabletOral3 mg
Tablet, coatedOral1 mg/1
Tablet, coatedOral2 mg/1
Tablet, coatedOral3 mg/1
Tablet, coatedOral2 mg
Tablet, film coatedOral3 mg
Capsule, liquid filledOral3 mg
Capsule, liquid filledOral1 mg
Capsule, liquid filledOral2 mg
Prices
Unit descriptionCostUnit
Lunesta 2 mg tablet8.08USD tablet
Lunesta 3 mg tablet7.28USD tablet
Lunesta 1 mg tablet7.24USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US6444673No2002-09-032014-02-14US flag
US6319926No2001-11-202012-01-16US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)202-203https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3711352.htm
boiling point (°C)487.2https://www.lookchem.com/Timolol/
water solubilitysoluble in waterhttps://www.chemicalbook.com/ChemicalProductProperty_EN_CB3711352.htm
logP0.81http://www.t3db.ca/toxins/T3D4552
pKa9.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.885 mg/mLALOGPS
logP0.97ALOGPS
logP0.81ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)13.04ChemAxon
pKa (Strongest Basic)6.89ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area91.76 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity95.89 m3·mol-1ChemAxon
Polarizability37.67 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9382
Caco-2 permeable+0.5805
P-glycoprotein substrateSubstrate0.6917
P-glycoprotein inhibitor IInhibitor0.6381
P-glycoprotein inhibitor IIInhibitor0.5
Renal organic cation transporterNon-inhibitor0.6785
CYP450 2C9 substrateNon-substrate0.7158
CYP450 2D6 substrateNon-substrate0.9115
CYP450 3A4 substrateSubstrate0.6775
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorInhibitor0.8995
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.689
Ames testAMES toxic0.5332
CarcinogenicityNon-carcinogens0.9174
BiodegradationNot ready biodegradable0.9941
Rat acute toxicity2.6411 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7838
hERG inhibition (predictor II)Non-inhibitor0.5688
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0190000000-979bdecccd14f99834e7

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Potentiator
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...
Gene Name
GABRA1
Uniprot ID
P14867
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-1
Molecular Weight
51801.395 Da
References
  1. Nutt DJ, Stahl SM: Searching for perfect sleep: the continuing evolution of GABAA receptor modulators as hypnotics. J Psychopharmacol. 2010 Nov;24(11):1601-12. doi: 10.1177/0269881109106927. Epub 2009 Nov 26. [Article]
  2. Hanson SM, Morlock EV, Satyshur KA, Czajkowski C: Structural requirements for eszopiclone and zolpidem binding to the gamma-aminobutyric acid type-A (GABAA) receptor are different. J Med Chem. 2008 Nov 27;51(22):7243-52. doi: 10.1021/jm800889m. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name
GABRA2
Uniprot ID
P47869
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-2
Molecular Weight
51325.85 Da
References
  1. Nutt DJ, Stahl SM: Searching for perfect sleep: the continuing evolution of GABAA receptor modulators as hypnotics. J Psychopharmacol. 2010 Nov;24(11):1601-12. doi: 10.1177/0269881109106927. Epub 2009 Nov 26. [Article]
  2. Hanson SM, Morlock EV, Satyshur KA, Czajkowski C: Structural requirements for eszopiclone and zolpidem binding to the gamma-aminobutyric acid type-A (GABAA) receptor are different. J Med Chem. 2008 Nov 27;51(22):7243-52. doi: 10.1021/jm800889m. [Article]
Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Positive allosteric modulator
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...

Components:
References
  1. Doble A, Canton T, Malgouris C, Stutzmann J, Piot O, Bardone M, Pauchet C, Blanchard J: The mechanism of action of zopiclone. Eur Psychiatry. 1995;10 Suppl 3:117s-28s. doi: 10.1016/0924-9338(96)80093-9. [Article]
  2. Wadworth AN, McTavish D: Zopiclone. A review of its pharmacological properties and therapeutic efficacy as an hypnotic. Drugs Aging. 1993 Sep-Oct;3(5):441-59. doi: 10.2165/00002512-199303050-00006. [Article]
  3. Dixon CL, Harrison NL, Lynch JW, Keramidas A: Zolpidem and eszopiclone prime alpha1beta2gamma2 GABAA receptors for longer duration of activity. Br J Pharmacol. 2015 Jul;172(14):3522-36. doi: 10.1111/bph.13142. Epub 2015 May 11. [Article]
  4. ChEMBL Compound Report Card [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name
GABRA3
Uniprot ID
P34903
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-3
Molecular Weight
55164.055 Da
References
  1. Nutt DJ, Stahl SM: Searching for perfect sleep: the continuing evolution of GABAA receptor modulators as hypnotics. J Psychopharmacol. 2010 Nov;24(11):1601-12. doi: 10.1177/0269881109106927. Epub 2009 Nov 26. [Article]
  2. Hanson SM, Morlock EV, Satyshur KA, Czajkowski C: Structural requirements for eszopiclone and zolpidem binding to the gamma-aminobutyric acid type-A (GABAA) receptor are different. J Med Chem. 2008 Nov 27;51(22):7243-52. doi: 10.1021/jm800889m. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Transporter activity
Specific Function
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name
GABRA5
Uniprot ID
P31644
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-5
Molecular Weight
52145.645 Da
References
  1. Nutt DJ, Stahl SM: Searching for perfect sleep: the continuing evolution of GABAA receptor modulators as hypnotics. J Psychopharmacol. 2010 Nov;24(11):1601-12. doi: 10.1177/0269881109106927. Epub 2009 Nov 26. [Article]
  2. Hanson SM, Morlock EV, Satyshur KA, Czajkowski C: Structural requirements for eszopiclone and zolpidem binding to the gamma-aminobutyric acid type-A (GABAA) receptor are different. J Med Chem. 2008 Nov 27;51(22):7243-52. doi: 10.1021/jm800889m. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  2. Lalovic B, Phillips B, Risler LL, Howald W, Shen DD: Quantitative contribution of CYP2D6 and CYP3A to oxycodone metabolism in human liver and intestinal microsomes. Drug Metab Dispos. 2004 Apr;32(4):447-54. [Article]
  3. Carlson JN, Haskew R, Wacker J, Maisonneuve IM, Glick SD, Jerussi TP: Sedative and anxiolytic effects of zopiclone's enantiomers and metabolite. Eur J Pharmacol. 2001 Mar;415(2-3):181-9. doi: 10.1016/s0014-2999(01)00851-2. [Article]
  4. Becquemont L, Mouajjah S, Escaffre O, Beaune P, Funck-Brentano C, Jaillon P: Cytochrome P-450 3A4 and 2C8 are involved in zopiclone metabolism. Drug Metab Dispos. 1999 Sep;27(9):1068-73. [Article]
  5. FDA Approved Drug Products: Lunesta (eszopiclone) oral tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  2. Lalovic B, Phillips B, Risler LL, Howald W, Shen DD: Quantitative contribution of CYP2D6 and CYP3A to oxycodone metabolism in human liver and intestinal microsomes. Drug Metab Dispos. 2004 Apr;32(4):447-54. [Article]
  3. Becquemont L, Mouajjah S, Escaffre O, Beaune P, Funck-Brentano C, Jaillon P: Cytochrome P-450 3A4 and 2C8 are involved in zopiclone metabolism. Drug Metab Dispos. 1999 Sep;27(9):1068-73. [Article]

Drug created at June 13, 2005 13:24 / Updated at December 04, 2021 10:33