Identification

Name
Clonazepam
Accession Number
DB01068  (APRD00054)
Type
Small Molecule
Groups
Approved, Illicit
Description

An anticonvulsant used for several types of seizures, including myotonic or atonic seizures, photosensitive epilepsy, and absence seizures, although tolerance may develop. It is seldom effective in generalized tonic-clonic or partial seizures. The mechanism of action appears to involve the enhancement of gamma-aminobutyric acid receptor responses. [PubChem]

Structure
Thumb
Synonyms
  • 1,3-dihydro-7-Nitro-5-(2-chlorophenyl)-2H-1,4.benzodiazepin-2-one
  • 5-(2-Chloro-phenyl)-7-nitro-1,3-dihydro-benzo[e][1,4]diazepin-2-one
  • 5-(2-Chlorophenyl)-7-nitro-1H-benzo[e][1,4]diazepin-2(3H)-one
  • 5-(O-Chlorophenyl)-7-nitro-1,3-dihydro-2H-1,4-benzodiazepin-2-one
  • CLONAZEPAM
  • Clonazepamum
External IDs
RO 5-4023 / RO-5-4023
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ClonapamTablet2.0 mgOralValeant Canada Lp Valeant Canada S.E.C.1997-02-28Not applicableCanada
ClonapamTablet0.5 mgOralValeant Canada Lp Valeant Canada S.E.C.1997-01-31Not applicableCanada
ClonapamTablet1.0 mgOralValeant Canada Lp Valeant Canada S.E.C.1997-01-31Not applicableCanada
ClonazepamTablet2 mg/1OralVintage Pharmaceuticals, LLC2006-10-182006-10-18Us
ClonazepamTablet1 mg/1OralWatson Pharmaceuticals2008-03-18Not applicableUs
ClonazepamTablet1 mgOralSivem Pharmaceuticals Ulc2015-07-09Not applicableCanada
ClonazepamTablet2 mgOralMeliapharm Inc2010-10-202014-06-25Canada
ClonazepamTablet2 mgOralSivem Pharmaceuticals Ulc2015-07-09Not applicableCanada
ClonazepamTablet1 mg/1OralVintage Pharmaceuticals, LLC2006-10-182006-10-18Us
ClonazepamTablet0.5 mgOralSivem Pharmaceuticals Ulc2015-07-09Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Accel-clonazepamTablet1.0 mgOralAccel Pharma IncNot applicableNot applicableCanada
Accel-clonazepamTablet0.5 mgOralAccel Pharma IncNot applicableNot applicableCanada
Accel-clonazepamTablet2.0 mgOralAccel Pharma IncNot applicableNot applicableCanada
Apo-clonazepam - Tab 0.5mgTablet.5 mgOralApotex Corporation1995-12-31Not applicableCanada
Apo-clonazepam - Tab 2mgTablet2 mgOralApotex Corporation1995-12-31Not applicableCanada
ClonazepamTablet1 mg/1OralRemedy Repack2014-06-172018-04-30Us
ClonazepamTablet1 mg/1OralUpsher Smith Laboratories2014-09-252017-08-31Us
ClonazepamTablet1 mg/1OralNucare Pharmaceuticals,inc.2011-06-03Not applicableUs
ClonazepamTablet2 mg/1OralGoldline Laboratories, Inc.2010-03-172010-03-18Us
ClonazepamTablet1 mg/1OralMc Kesson2007-08-02Not applicableUs
International/Other Brands
Antelepsin (AWD) / Iktorivil (Roche) / Rivotril (Roche)
Categories
UNII
5PE9FDE8GB
CAS number
1622-61-3
Weight
Average: 315.711
Monoisotopic: 315.041068908
Chemical Formula
C15H10ClN3O3
InChI Key
DGBIGWXXNGSACT-UHFFFAOYSA-N
InChI
InChI=1S/C15H10ClN3O3/c16-12-4-2-1-3-10(12)15-11-7-9(19(21)22)5-6-13(11)18-14(20)8-17-15/h1-7H,8H2,(H,18,20)
IUPAC Name
5-(2-chlorophenyl)-7-nitro-2,3-dihydro-1H-1,4-benzodiazepin-2-one
SMILES
[O-][N+](=O)C1=CC2=C(NC(=O)CN=C2C2=CC=CC=C2Cl)C=C1

Pharmacology

Indication

Clonazepam is used as an anticonvulsant in the treatment of the Lennox-Gastaut syndrome (petit mal variant), akinetic and myoclonic seizures. It can also be used for the treatment of panic disorders.

Associated Conditions
Pharmacodynamics

Clonazepam, a benzodiazepine, is used primarily as an anticonvulsant in the treatment of absence seizures, petit mal variant seizures (Lennox-Gastaut syndrome), akinetic and myoclonic seizures, and nocturnal myoclonus. It enhances the activity of gamma aminobutyric acid (GABA), which is a major inhibitory neurotransmitter in the central nervous system. In animals, convulsions are antagonized occurs following administration of clonazepam. In humans, clonazepam suppresses the spike and wave discharge in absence seizures (petit mal) and decreases the frequency, amplitude, duration, and spread of discharge in minor motor seizures.

Mechanism of action

Allosteric interactions between central benzodiazepine receptors and gamma-aminobutyric acid (GABA) receptors potentiate the effects of GABA. As GABA is an inhibitory neurotransmitter, this results in increased inhibition of the ascending reticular activating system. Benzodiazepines, in this way, block the cortical and limbic arousal that occurs following stimulation of the reticular pathways.

TargetActionsOrganism
AGABA-A receptor (anion channel)
positive allosteric modulator
Human
UTranslocator protein
other/unknown
Human
UNuclear receptor subfamily 1 group I member 2
partial agonist
Human
Absorption

Clonazepam is rapidly and completely absorbed after oral administration. The absolute bioavailability of clonazepam is about 90%. Cmax, oral administration = 1 -4 hours.

Volume of distribution
Not Available
Protein binding

85% bound to plasma proteins.

Metabolism

Hepatic (cytochrome P450, including CYP3A). Biotransformation occurs mainly by reduction of the 7-nitro group to the 4-amino derivative. This derivative can be acetylated, hydroxylated, and glucuronidated.

Route of elimination

Clonazepam is highly metabolized, with less than 2% unchanged clonazepam being excreted in the urine. Metabolites of Klonopin are excreted by the kidneys. Clonazepam also undergoes acetylation via NAT2.

Half life

30-40 hours

Clearance
Not Available
Toxicity

Somnolence, confusion, coma, and diminished reflexes. The most commonly reported adverse event when clonazepam is used for seizure disorders is CNS depression.
LD50, oral, rats = >15000 mg/kg.

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 Clonazepam.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Clonazepam.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Clonazepam is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe therapeutic efficacy of Clonazepam can be decreased when used in combination with 3-isobutyl-1-methyl-7H-xanthine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when Clonazepam is combined with 3,4-Methylenedioxyamphetamine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Clonazepam.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Clonazepam is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Clonazepam.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Clonazepam is combined with 4-Methoxyamphetamine.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Clonazepam.
Food Interactions
  • Avoid alcohol.
  • Avoid excessive quantities of coffee or tea (Caffeine).
  • Take without regard to meals.

References

Synthesis Reference

Kariss, J. and Newmark, H.L.; US. Patents 3,116,203; December 31, 1963; and 3,123,529; March 3, 1964; both assigned to Hoffmann-LaRoche, Inc. Keller, O., Steiger, N. and Sternbach, L.H.; U S . Patents 3,121,114; February 11, 1964; and 3,203890; August 31, 1965; both assigned to Hoffmann-LaRoche, Inc. Focella, A. and Rachlin, A.I.; U.S. Patent 3,335,181; August 8, 1967; assigned to Hoffmann- LaRoche. Inc.

General References
  1. Dreifuss FE, Penry JK, Rose SW, Kupferberg HJ, Dyken P, Sato S: Serum clonazepam concentrations in children with absence seizures. Neurology. 1975 Mar;25(3):255-8. [PubMed:1089913]
  2. Robertson MD, Drummer OH: Postmortem drug metabolism by bacteria. J Forensic Sci. 1995 May;40(3):382-6. [PubMed:7782744]
  3. Rosen GM, Turner MJ 3rd: Synthesis of spin traps specific for hydroxyl radical. J Med Chem. 1988 Feb;31(2):428-32. [PubMed:2828624]
  4. Rosen GM, Demos HA, Rauckman EJ: Not all aromatic nitro compounds form free radicals. Toxicol Lett. 1984 Aug;22(2):145-52. [PubMed:6089382]
  5. Earley JV, Fryer RI, Ning RY: Quinazolines and 1,4-benzodiazepines. LXXXIX: Haptens useful in benzodiazepine immunoassay development. J Pharm Sci. 1979 Jul;68(7):845-50. [PubMed:458601]
External Links
Human Metabolome Database
HMDB0015201
KEGG Drug
D00280
PubChem Compound
2802
PubChem Substance
46507677
ChemSpider
2700
BindingDB
50019213
ChEBI
3756
ChEMBL
CHEMBL452
Therapeutic Targets Database
DAP000259
PharmGKB
PA449050
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Clonazepam
ATC Codes
N03AE01 — Clonazepam
AHFS Codes
  • 28:12.08 — Benzodiazepines
MSDS
Download (74.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedTreatmentBurning Mouth Syndrome1
1CompletedNot AvailablePharmacokinetics1
1CompletedNot AvailableTo Determine Bioequivalence Under Fasting Conditions2
1RecruitingTreatmentPain, Neuropathic1
1, 2CompletedBasic SciencePain, Neuropathic1
2CompletedTreatmentEpilepsies1
2CompletedTreatmentREM Sleep Behavior Disorder1
2Not Yet RecruitingTreatmentParkinson's Disease (PD) / REM Sleep Behavior Disorder1
2RecruitingTreatmentCannabis Use Disorders1
2, 3CompletedTreatmentPanic Disorders1
3CompletedTreatmentEpilepsies / Refractory seizure disorders1
3CompletedTreatmentPain NOS1
3CompletedTreatmentStatus; Epilepticus, Tonic-clonic1
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1
3TerminatedTreatmentEpilepsia Partialis Continua / Epilepsies / Kojewnikov's Epilepsy1
4CompletedTreatmentFear of open spaces / Panic Disorders1
4CompletedTreatmentPost Traumatic Stress Disorder (PTSD)1
4CompletedTreatmentSocial Phobia1
4RecruitingDiagnosticSevere Major Depression Disorder1
4RecruitingTreatmentEpilepsies1
4Unknown StatusTreatmentCardiac Arrest1
4WithdrawnTreatmentBurning Mouth Syndrome1
4WithdrawnTreatmentSchizoaffective Disorders / Schizophrenic Disorders / Schizophreniform Disorder1
Not AvailableRecruitingTreatmentREM Sleep Behavior Disorder1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Actavis Group
  • Aidarex Pharmacuticals LLC
  • Alphapharm Party Ltd.
  • Apotex Inc.
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • Barr Pharmaceuticals
  • Bryant Ranch Prepack
  • Caraco Pharmaceutical Labs
  • Cardinal Health
  • Caremark LLC
  • Catalent Pharma Solutions
  • Cebert Pharmaceuticals Inc.
  • Centaur Pharmaceuticals Pvt Ltd.
  • Comprehensive Consultant Services Inc.
  • Corepharma LLC
  • Coupler Enterprises Inc.
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Eon Labs
  • F Hoffmann-La Roche Ltd.
  • Golden State Medical Supply Inc.
  • Goldline Laboratories Inc.
  • H.J. Harkins Co. Inc.
  • Heartland Repack Services LLC
  • Innoviant Pharmacy Inc.
  • Kali Laboratories Inc.
  • Keltman Pharmaceuticals Inc.
  • Lake Erie Medical and Surgical Supply
  • Liberty Pharmaceuticals
  • Major Pharmaceuticals
  • Mckesson Corp.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Novopharm Ltd.
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • Par Pharmaceuticals
  • PD-Rx Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Qualitest
  • Rebel Distributors Corp.
  • Recalcine Laboratorios
  • Redpharm Drug
  • Remedy Repack
  • Sandhills Packaging Inc.
  • Sanofi-Aventis Inc.
  • Southwood Pharmaceuticals
  • St Mary's Medical Park Pharmacy
  • Stat Rx Usa
  • Syntex SA
  • Teva Pharmaceutical Industries Ltd.
  • Torpharm Inc.
  • UDL Laboratories
  • Va Cmop Dallas
  • Vintage Pharmaceuticals Inc.
Dosage forms
FormRouteStrength
TabletOral1.0 mg
TabletOral2.0 mg
TabletOral.5 mg
TabletOral0.5 mg/1
TabletOral1 mg/1
TabletOral2 mg/1
Tablet, orally disintegratingOral.25 mg/1
Tablet, orally disintegratingOral.5 mg/1
Tablet, orally disintegratingOral0.125 mg/1
Tablet, orally disintegratingOral0.25 mg/1
Tablet, orally disintegratingOral0.5 mg/1
Tablet, orally disintegratingOral1 mg/1
Tablet, orally disintegratingOral2 mg/1
TabletOral.5 mg/1
WaferOral0.125 mg/1
WaferOral0.25 mg/1
WaferOral0.5 mg/1
WaferOral1 mg/1
WaferOral2 mg/1
TabletOral0.5 mg
TabletOral1 mg
TabletOral2 mg
TabletOral0.25 mg
Prices
Unit descriptionCostUnit
Klonopin 2 mg tablet2.85USD tablet
Klonopin 1 mg tablet2.17USD tablet
Klonopin 0.5 mg tablet1.91USD tablet
ClonazePAM ODT 2 mg Dispersible Tablet1.67USD dispersible tablet
ClonazePAM ODT 0.25 mg Dispersible Tablet1.22USD dispersible tablet
ClonazePAM ODT 0.5 mg Dispersible Tablet1.18USD dispersible tablet
ClonazePAM ODT 0.125 mg Dispersible Tablet1.17USD dispersible tablet
ClonazePAM ODT 1 mg Dispersible Tablet1.1USD dispersible tablet
Clonazepam 2 mg tablet0.81USD tablet
Clonazepam 1 mg tablet0.63USD tablet
Clonazepam 0.5 mg tablet0.61USD tablet
Rivotril 2 mg Tablet0.38USD tablet
Rivotril 0.5 mg Tablet0.22USD tablet
Apo-Clonazepam 2 mg Tablet0.21USD tablet
Co Clonazepam 2 mg Tablet0.21USD tablet
Mylan-Clonazepam 2 mg Tablet0.21USD tablet
Novo-Clonazepam 2 mg Tablet0.21USD tablet
Phl-Clonazepam 2 mg Tablet0.21USD tablet
Pms-Clonazepam 2 mg Tablet0.21USD tablet
Ratio-Clonazepam 2 mg Tablet0.21USD tablet
Sandoz Clonazepam 2 mg Tablet0.21USD tablet
Co Clonazepam 1 mg Tablet0.19USD tablet
Phl-Clonazepam 1 mg Tablet0.19USD tablet
Pms-Clonazepam 1 mg Tablet0.19USD tablet
Sandoz Clonazepam 1 mg Tablet0.19USD tablet
Apo-Clonazepam 0.5 mg Tablet0.12USD tablet
Co Clonazepam 0.5 mg Tablet0.12USD tablet
Mylan-Clonazepam 0.5 mg Tablet0.12USD tablet
Novo-Clonazepam 0.5 mg Tablet0.12USD tablet
Phl-Clonazepam 0.5 mg Tablet0.12USD tablet
Phl-Clonazepam-R 0.5 mg Tablet0.12USD tablet
Pms-Clonazepam 0.5 mg Tablet0.12USD tablet
Pms-Clonazepam-R 0.5 mg Tablet0.12USD tablet
Ratio-Clonazepam 0.5 mg Tablet0.12USD tablet
Sandoz Clonazepam 0.5 mg Tablet0.12USD tablet
Pms-Clonazepam 0.25 mg Tablet0.07USD 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)238-240Kariss, J. and Newmark, H.L.; US. Patents 3,116,203; December 31, 1963; and 3,123,529; March 3, 1964; both assigned to Hoffmann-LaRoche, Inc. Keller, O., Steiger, N. and Sternbach, L.H.; U S . Patents 3,121,114; February 11, 1964; and 3,203890; August 31, 1965; both assigned to Hoffmann-LaRoche, Inc. Focella, A. and Rachlin, A.I.; U.S. Patent 3,335,181; August 8, 1967; assigned to Hoffmann- LaRoche. Inc.
water solubility100 mg/L (at 25 °C)MERCK INDEX (1996)
logP2.41HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.0106 mg/mLALOGPS
logP2.76ALOGPS
logP3.15ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)11.89ChemAxon
pKa (Strongest Basic)1.86ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area87.28 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity84.02 m3·mol-1ChemAxon
Polarizability29.59 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9946
Blood Brain Barrier+0.9718
Caco-2 permeable+0.5313
P-glycoprotein substrateSubstrate0.5594
P-glycoprotein inhibitor INon-inhibitor0.8474
P-glycoprotein inhibitor IINon-inhibitor0.9157
Renal organic cation transporterNon-inhibitor0.8179
CYP450 2C9 substrateNon-substrate0.7777
CYP450 2D6 substrateNon-substrate0.8934
CYP450 3A4 substrateSubstrate0.7295
CYP450 1A2 substrateInhibitor0.7646
CYP450 2C9 inhibitorInhibitor0.5213
CYP450 2D6 inhibitorNon-inhibitor0.8271
CYP450 2C19 inhibitorInhibitor0.7441
CYP450 3A4 inhibitorInhibitor0.5565
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7255
Ames testNon AMES toxic0.6778
CarcinogenicityNon-carcinogens0.6417
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.6422 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9821
hERG inhibition (predictor II)Non-inhibitor0.8734
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)MSsplash10-02a9-2492000000-109e2626e8a128b9e433
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as 1,4-benzodiazepines. These are organic compounds containing a benzene ring fused to a 1,4-azepine.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzodiazepines
Sub Class
1,4-benzodiazepines
Direct Parent
1,4-benzodiazepines
Alternative Parents
Nitroaromatic compounds / Chlorobenzenes / Aryl chlorides / Cyclic carboximidic acids / Ketimines / Propargyl-type 1,3-dipolar organic compounds / Organic oxoazanium compounds / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds
show 4 more
Substituents
1,4-benzodiazepine / Nitroaromatic compound / Chlorobenzene / Halobenzene / Aryl chloride / Aryl halide / Monocyclic benzene moiety / Benzenoid / Cyclic carboximidic acid / Ketimine
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
monochlorobenzenes, 1,4-benzodiazepinone (CHEBI:3756)

Targets

Kind
Protein group
Organism
Human
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. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [PubMed:11752090]
  2. Riss J, Cloyd J, Gates J, Collins S: Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008 Aug;118(2):69-86. doi: 10.1111/j.1600-0404.2008.01004.x. Epub 2008 Mar 31. [PubMed:18384456]
Details
2. Translocator protein
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Other/unknown
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. Carmel I, Fares FA, Leschiner S, Scherubl H, Weisinger G, Gavish M: Peripheral-type benzodiazepine receptors in the regulation of proliferation of MCF-7 human breast carcinoma cell line. Biochem Pharmacol. 1999 Jul 15;58(2):273-8. [PubMed:10423168]
  2. Bono F, Lamarche I, Prabonnaud V, Le Fur G, Herbert JM: Peripheral benzodiazepine receptor agonists exhibit potent antiapoptotic activities. Biochem Biophys Res Commun. 1999 Nov 19;265(2):457-61. [PubMed:10558889]
  3. Bolger GT, Abraham S, Oz N, Weissman BA: Interactions between peripheral-type benzodiazepine receptor ligands and an activator of voltage-operated calcium channels. Can J Physiol Pharmacol. 1990 Jan;68(1):40-5. [PubMed:1691678]
  4. Marano G, Massotti M, Spagnolo A, Carpi A: Enhancement of pharmacologically induced bronchoconstriction by Ro 5-4864. Eur J Pharmacol. 1990 Apr 10;179(1-2):237-40. [PubMed:2364987]
  5. Awad M, Gavish M: Solubilization of peripheral-type benzodiazepine binding sites from cat cerebral cortex. J Neurochem. 1989 Jun;52(6):1880-5. [PubMed:2723642]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Partial agonist
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism an...
Gene Name
NR1I2
Uniprot ID
O75469
Uniprot Name
Nuclear receptor subfamily 1 group I member 2
Molecular Weight
49761.245 Da
References
  1. Creusot N, Kinani S, Balaguer P, Tapie N, LeMenach K, Maillot-Marechal E, Porcher JM, Budzinski H, Ait-Aissa S: Evaluation of an hPXR reporter gene assay for the detection of aquatic emerging pollutants: screening of chemicals and application to water samples. Anal Bioanal Chem. 2010 Jan;396(2):569-83. doi: 10.1007/s00216-009-3310-y. Epub 2009 Nov 29. [PubMed:20024649]

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. 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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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. Tassaneeyakul W, Birkett DJ, Miners JO: Inhibition of human hepatic cytochrome P4502E1 by azole antifungals, CNS-active drugs and non-steroidal anti-inflammatory agents. Xenobiotica. 1998 Mar;28(3):293-301. [PubMed:9574817]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Arylamine n-acetyltransferase activity
Specific Function
Participates in the detoxification of a plethora of hydrazine and arylamine drugs. Catalyzes the N- or O-acetylation of various arylamine and heterocyclic amine substrates and is able to bioactivat...
Gene Name
NAT2
Uniprot ID
P11245
Uniprot Name
Arylamine N-acetyltransferase 2
Molecular Weight
33542.235 Da
References
  1. Olivera M, Martinez C, Gervasini G, Carrillo JA, Ramos S, Benitez J, Garcia-Martin E, Agundez JA: Effect of common NAT2 variant alleles in the acetylation of the major clonazepam metabolite, 7-aminoclonazepam. Drug Metab Lett. 2007 Jan;1(1):3-5. [PubMed:19356010]
  2. Miller ME, Garland WA, Min BH, Ludwick BT, Ballard RH, Levy RH: Clonazepam acetylation in fast and slow acetylators. Clin Pharmacol Ther. 1981 Sep;30(3):343-7. [PubMed:7273597]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
No
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Pacifici GM, Viani A, Rizzo G, Carrai M, Rane A: Plasma protein binding of clonazepam in hepatic and renal insufficiency and after hemodialysis. Ther Drug Monit. 1987 Dec;9(4):369-73. [PubMed:3424402]

Drug created on June 13, 2005 07:24 / Updated on November 21, 2018 07:14