Identification

Name
Zopiclone
Accession Number
DB01198  (APRD00356)
Type
Small Molecule
Groups
Approved
Description

Zopiclone is a novel hypnotic agent used in the treatment of insomnia. Its mechanism of action is based on modulating benzodiazepine receptors. In addition to zopiclone's benzodiazepine pharmacological properties it also has some barbiturate like properties.

Structure
Thumb
Synonyms
  • (+-)-zopiclone
  • (±)-zopiclone
  • 6-(5-Chloro-2-pyridinyl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-yl 4-methyl-1-piperazinecarboxylate
  • Zopiclona
  • Zopiclone
  • Zopiclonum
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act ZopicloneTablet7.5 mgOralActavis Pharma Company2005-11-11Not applicableCanada
Act ZopicloneTablet5 mgOralActavis Pharma Company2005-11-11Not applicableCanada
ImovaneTablet5.0 mgOralSanofi Aventis1998-02-10Not applicableCanada
Imovane 7.5 - Tab 7.5mgTablet7.5 mgOralSanofi Aventis1990-12-31Not applicableCanada
M-zopicloneTablet5 mgOralMantra Pharma IncNot applicableNot applicableCanada
M-zopicloneTablet7.5 mgOralMantra Pharma IncNot applicableNot applicableCanada
Q-zopicloneTablet5 mgOralQd Pharmaceuticals UlcNot applicableNot applicableCanada
Q-zopicloneTablet7.5 mgOralQd Pharmaceuticals Ulc2011-11-242015-08-21Canada
Riva ZopicloneTablet7.5 mgOralLaboratoire Riva Inc2008-11-14Not applicableCanada
Riva ZopicloneTablet5 mgOralLaboratoire Riva Inc2006-10-10Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-zopicloneTablet5 mgOralApotex Corporation2002-06-04Not applicableCanada
Apo-zopiclone - Tab 7.5mgTablet7.5 mgOralApotex Corporation1996-09-19Not applicableCanada
Ava-zopicloneTablet7.5 mgOralAvanstra Inc2011-09-092014-08-21Canada
Ava-zopicloneTablet5 mgOralAvanstra Inc2011-08-112014-08-21Canada
Dom-zopicloneTablet5 mgOralDominion Pharmacal2009-05-25Not applicableCanada
Dom-zopicloneTablet7.5 mgOralDominion Pharmacal1999-11-23Not applicableCanada
Ipg-zopicloneTablet5 mgOralMarcan Pharmaceuticals IncNot applicableNot applicableCanada
Ipg-zopicloneTablet3.75 mgOralMarcan Pharmaceuticals IncNot applicableNot applicableCanada
Ipg-zopicloneTablet7.5 mgOralMarcan Pharmaceuticals IncNot applicableNot applicableCanada
Jamp-zopicloneTablet7.5 mgOralJamp Pharma Corporation2011-11-02Not applicableCanada
International/Other Brands
Amoban / Imovane / Zimovane
Categories
UNII
03A5ORL08Q
CAS number
43200-80-2
Weight
Average: 388.808
Monoisotopic: 388.105066147
Chemical Formula
C17H17ClN6O3
InChI Key
GBBSUAFBMRNDJC-UHFFFAOYSA-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
IUPAC Name
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)OC1N(C(=O)C2=NC=CN=C12)C1=NC=C(Cl)C=C1

Pharmacology

Indication

For the short-term treatment of insomnia.

Associated Conditions
Pharmacodynamics

Zopiclone is a nonbenzodiazepine hypnotic from the pyrazolopyrimidine class and is indicated for the short-term treatment of insomnia. While Zopiclone 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. Zopiclone binds selectively to the brain alpha subunit of the GABA A omega-1 receptor.

Mechanism of action

Zopiclone exerts its action by binding on the benzodiazepine receptor complex and modulation of the GABABZ receptor chloride channel macromolecular complex. Both zopiclone and benzodiazepines act indiscriminately at the benzodiazepine binding site on α1, α2, α3 and α5 GABAA containing receptors as full agonists causing an enhancement of the inhibitory actions of GABA to produce the therapeutic (hypnotic and anxiolytic) and adverse effects of zopiclone.

TargetActionsOrganism
AGamma-aminobutyric acid receptor subunit alpha-1
potentiator
Human
AGamma-aminobutyric acid receptor subunit alpha-2
potentiator
Human
AGamma-aminobutyric acid receptor subunit alpha-3
potentiator
Human
AGamma-aminobutyric acid receptor subunit alpha-5
potentiator
Human
UTranslocator protein
agonist
Human
Absorption

Rapidly absorbed following oral administration.

Volume of distribution
Not Available
Protein binding

Approximately 45%

Metabolism

Extensively metabolized in the liver via decarboxylation (major pathway), demethylation, and side chain oxidation. Metabolites include an N-oxide derivative (weakly active; approximately 12% of a dose) and an N-desmethyl metabolite (inactive; approximately 16%). Approximately 50% of a dose is converted to other inactive metabolites via decarboxylation. Hepatic microsomal enzymes are apparently not involved in zopiclone clearance.

Route of elimination
Not Available
Half life

Elimination half life is approximately 5 hours (range 3.8 to 6.5 hours) and is prolonged to 11.9 hours in patients with hepatic insufficiency.

Clearance
Not Available
Toxicity

Rare individual instances of fatal outcomes following overdose with racemic zopiclone have been reported in European postmarketing reports, most often associated with overdose with other CNS-depressant agent. Signs and symptoms of overdose effects of CNS depressants can be expected to present as exaggerations of the pharmacological effects noted in preclinical testing.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Zopiclone.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Zopiclone.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when 2,5-Dimethoxy-4-ethylthioamphetamine is combined with Zopiclone.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when 3,4-Methylenedioxyamphetamine is combined with Zopiclone.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Zopiclone.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Zopiclone.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Zopiclone.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Zopiclone.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Zopiclone.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when 5-methoxy-N,N-dimethyltryptamine is combined with Zopiclone.
Food Interactions
Not Available

References

Synthesis Reference

Thomas Jerussi, "Compositions comprising zopiclone derivatives and methods of making and using the same." U.S. Patent US20040147521, issued July 29, 2004.

US20040147521
General References
  1. Liu HJ, Sato K, Shih HC, Shibuya T, Kawamoto H, Kitagawa H: Pharmacologic studies of the central action of zopiclone: effects on locomotor activity and brain monoamines in rats. Int J Clin Pharmacol Ther Toxicol. 1985 Mar;23(3):121-8. [PubMed:2581904]
  2. Sato K, Hong YL, Yang MS, Shibuya T, Kawamoto H, Kitagawa H: Pharmacologic studies of central actions of zopiclone: influence on brain monoamines in rats under stressful condition. Int J Clin Pharmacol Ther Toxicol. 1985 Apr;23(4):204-10. [PubMed:2860074]
  3. Dundar Y, Dodd S, Strobl J, Boland A, Dickson R, Walley T: Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and meta-analysis. Hum Psychopharmacol. 2004 Jul;19(5):305-22. [PubMed:15252823]
  4. Blanchard JC, Julou L: Suriclone: a new cyclopyrrolone derivative recognizing receptors labeled by benzodiazepines in rat hippocampus and cerebellum. J Neurochem. 1983 Mar;40(3):601-7. [PubMed:6298365]
  5. Julou L, Bardone MC, Blanchard JC, Garret C, Stutzmann JM: Pharmacological studies on zopiclone. Pharmacology. 1983;27 Suppl 2:46-58. [PubMed:6142468]
External Links
Human Metabolome Database
HMDB0015329
KEGG Drug
D01372
PubChem Compound
5735
PubChem Substance
46505233
ChemSpider
5533
BindingDB
50054136
ChEBI
32315
ChEMBL
CHEMBL135400
Therapeutic Targets Database
DAP000427
PharmGKB
PA10236
Drugs.com
Drugs.com Drug Page
Wikipedia
Zopiclone
ATC Codes
N05CF01 — Zopiclone
AHFS Codes
  • 28:24.92 — Miscellaneous Anxiolytics Sedatives and Hypnotics

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedTreatmentParkinson's Disease (PD) / Sleeplessness1
1CompletedBasic ScienceHealthy Participants1
1CompletedPreventionSleeplessness1
1CompletedTreatmentPsychiatric Disorder NOS / Sleep Initiation and Maintenance Disorders1
1CompletedTreatmentSleeplessness2
1Not Yet RecruitingBasic ScienceAlcohol Drinking / Healthy Volunteers1
2CompletedTreatmentInsomnia Chronic1
3CompletedTreatmentBalance1
3CompletedTreatmentHealthy Volunteers / Sleep Initiation and Maintenance Disorders1
3CompletedTreatmentObstructive Sleep Apnea (OSA)1
3CompletedTreatmentSleep1
3CompletedTreatmentSleeplessness1
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1
4CompletedTreatmentFeeling Anxious1
4CompletedTreatmentSleeplessness1
4RecruitingSupportive CareSleep Apnea, Central / Ventricular Dysfunction1
4RecruitingTreatmentSleep / Sleeplessness1
Not AvailableCompletedDiagnosticCardiac Dysrhythmia / Chronic Obstructive / Hypercapnia / Hypoxemia / Pulmonary Diseases1
Not AvailableRecruitingTreatmentHip Pain Chronic1
Not AvailableWithdrawnNot AvailableAutomobile Driving1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Centaur Pharmaceuticals Pvt Ltd.
Dosage forms
FormRouteStrength
TabletOral5 mg
TabletOral5.0 mg
TabletOral7.5 mg
TabletOral3.75 mg
Prices
Unit descriptionCostUnit
Imovane 7.5 mg Tablet1.41USD tablet
Imovane 5 mg Tablet1.11USD tablet
Apo-Zopiclone 7.5 mg Tablet0.49USD tablet
Co Zopiclone 7.5 mg Tablet0.49USD tablet
Mylan-Zopiclone 7.5 mg Tablet0.49USD tablet
Novo-Zopiclone 7.5 mg Tablet0.49USD tablet
Nu-Zopiclone 7.5 mg Tablet0.49USD tablet
Pms-Zopiclone 7.5 mg Tablet0.49USD tablet
Ran-Zopiclone 7.5 mg Tablet0.49USD tablet
Ratio-Zopiclone 7.5 mg Tablet0.49USD tablet
Rhovane 7.5 mg Tablet0.49USD tablet
Sandoz Zopiclone 7.5 mg Tablet0.49USD tablet
Zopiclone 7.5 mg Tablet0.49USD tablet
Apo-Zopiclone 5 mg Tablet0.23USD tablet
Co Zopiclone 5 mg Tablet0.23USD tablet
Mylan-Zopiclone 5 mg Tablet0.23USD tablet
Novo-Zopiclone 5 mg Tablet0.23USD tablet
Pms-Zopiclone 5 mg Tablet0.23USD tablet
Ran-Zopiclone 5 mg Tablet0.23USD tablet
Ratio-Zopiclone 5 mg Tablet0.23USD tablet
Sandoz Zopiclone 5 mg Tablet0.23USD tablet
Zopiclone 5 mg Tablet0.23USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)178 °CPhysProp
water solubility0.151 mg/mL at 25 °CMEYLAN,WM et al. (1996)
logP0.8Not 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
Mass Spectrum (Electron Ionization)MSsplash10-0007-6950000000-c1583a92e3cbc5066186
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
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00kb-0090000000-9d80e08080f406848221
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-0092000000-977d45f9a516242be80f
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-0090000000-397a508c11f66c161327
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014j-0090000000-abc6a676659114a83d08
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0790000000-74d7c73e854e61700433
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00lr-0920000000-2c17f6282d1031cb4d50
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-0900000000-c0f92aba9374337ff737
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-003r-5900000000-46755df8b5cfb7f46bf9
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-004i-9300000000-091d5434bc674d5bf9a4
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-004i-9000000000-87365fa01fb0854897ca
13C NMR Spectrum1D NMRNot Applicable

Taxonomy

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
Cyclopyrrolone / Piperazine-1-carboxylic acid / 2-heteroaryl carboxamide / N-methylpiperazine / N-alkylpiperazine / Aryl chloride / Aryl halide / Imidolactam / Pyridine / Pyrazine
show 25 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
pyrrolopyrazine, monochloropyridine (CHEBI:32315)

Targets

Kind
Protein
Organism
Human
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. [PubMed:19942638]
  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. [PubMed:18973287]
  3. Sanger DJ: The pharmacology and mechanisms of action of new generation, non-benzodiazepine hypnotic agents. CNS Drugs. 2004;18 Suppl 1:9-15; discussion 41, 43-5. [PubMed:15291009]
  4. Skerritt JH, Johnston GA: Enhancement of GABA binding by benzodiazepines and related anxiolytics. Eur J Pharmacol. 1983 May 6;89(3-4):193-8. [PubMed:6135616]
  5. Ramerstorfer J, Furtmuller R, Vogel E, Huck S, Sieghart W: The point mutation gamma 2F77I changes the potency and efficacy of benzodiazepine site ligands in different GABAA receptor subtypes. Eur J Pharmacol. 2010 Jun 25;636(1-3):18-27. doi: 10.1016/j.ejphar.2010.03.015. Epub 2010 Mar 19. [PubMed:20303942]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Potentiator
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. [PubMed:19942638]
  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. [PubMed:18973287]
  3. Ramerstorfer J, Furtmuller R, Vogel E, Huck S, Sieghart W: The point mutation gamma 2F77I changes the potency and efficacy of benzodiazepine site ligands in different GABAA receptor subtypes. Eur J Pharmacol. 2010 Jun 25;636(1-3):18-27. doi: 10.1016/j.ejphar.2010.03.015. Epub 2010 Mar 19. [PubMed:20303942]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Potentiator
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. [PubMed:19942638]
  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. [PubMed:18973287]
  3. Ramerstorfer J, Furtmuller R, Vogel E, Huck S, Sieghart W: The point mutation gamma 2F77I changes the potency and efficacy of benzodiazepine site ligands in different GABAA receptor subtypes. Eur J Pharmacol. 2010 Jun 25;636(1-3):18-27. doi: 10.1016/j.ejphar.2010.03.015. Epub 2010 Mar 19. [PubMed:20303942]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Potentiator
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. [PubMed:19942638]
  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. [PubMed:18973287]
  3. Skerritt JH, Johnston GA: Enhancement of GABA binding by benzodiazepines and related anxiolytics. Eur J Pharmacol. 1983 May 6;89(3-4):193-8. [PubMed:6135616]
  4. Ramerstorfer J, Furtmuller R, Vogel E, Huck S, Sieghart W: The point mutation gamma 2F77I changes the potency and efficacy of benzodiazepine site ligands in different GABAA receptor subtypes. Eur J Pharmacol. 2010 Jun 25;636(1-3):18-27. doi: 10.1016/j.ejphar.2010.03.015. Epub 2010 Mar 19. [PubMed:20303942]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Cholesterol binding
Specific Function
Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Promotes the transport of cholesterol across mitochondrial membranes and may play a role in l...
Gene Name
TSPO
Uniprot ID
P30536
Uniprot Name
Translocator protein
Molecular Weight
18827.81 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]

Enzymes

Kind
Protein
Organism
Human
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. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. 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. [PubMed:15039299]
Kind
Protein
Organism
Human
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. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. 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. [PubMed:15039299]
Kind
Protein
Organism
Human
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
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 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. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 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. [PubMed:19515014]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on June 13, 2005 07:24 / Updated on November 12, 2018 07:28