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Identification
NameClonazepam
Accession NumberDB01068  (APRD00054)
TypeSmall Molecule
GroupsApproved, 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
SynonymLanguageCode
1,3-dihydro-7-Nitro-5-(2-chlorophenyl)-2H-1,4.benzodiazepin-2-oneNot AvailableNot Available
5-(2-Chloro-phenyl)-7-nitro-1,3-dihydro-benzo[e][1,4]diazepin-2-oneNot AvailableNot Available
5-(2-Chlorophenyl)-7-nitro-1H-benzo[e][1,4]diazepin-2(3H)-oneNot AvailableNot Available
5-(O-Chlorophenyl)-7-nitro-1,3-dihydro-2H-1,4-benzodiazepin-2-oneNot AvailableNot Available
CLONAZEPAMNot AvailableNot Available
ClonazepamumNot AvailableINN
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Klonopintablet1 mgoralGenentech, Inc.1975-06-02Not AvailableUs
Klonopintablet.5 mgoralGenentech, Inc.1975-06-02Not AvailableUs
Klonopintablet2 mgoralGenentech, Inc.1975-06-02Not AvailableUs
Klonopintablet.5 mgoralSTAT Rx USA LLC1975-06-02Not AvailableUs
Klonopintablet1 mgoralSTAT Rx USA LLC1975-06-02Not AvailableUs
Klonopintablet.5 mgoralCardinal Health1982-01-01Not AvailableUs
Klonopintablet1 mgoralCardinal Health1982-01-01Not AvailableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Clonazepamtablet.5 mgoralTeva Pharmaceuticals USA Inc1996-09-18Not AvailableUs
Clonazepamtablet1 mgoralTeva Pharmaceuticals USA Inc1996-09-17Not AvailableUs
Clonazepamtablet2 mgoralTeva Pharmaceuticals USA Inc1996-09-18Not AvailableUs
Clonazepamtablet.5 mgoralKAISER FOUNDATION HOSPITALS2014-11-11Not AvailableUs
Clonazepamtablet.5 mgoralEon Labs, Inc.1997-08-29Not AvailableUs
Clonazepamtablet1 mgoralEon Labs, Inc.1997-08-29Not AvailableUs
Clonazepamtablet2 mgoralEon Labs, Inc.1997-08-29Not AvailableUs
Clonazepamtablet.5 mgoralActavis Elizabeth LLC2009-02-13Not AvailableUs
Clonazepamtablet1 mgoralActavis Elizabeth LLC2009-02-13Not AvailableUs
Clonazepamtablet2 mgoralActavis Elizabeth LLC2009-02-13Not AvailableUs
Clonazepamtablet.5 mgoralMylan Pharmaceuticals Inc.1998-10-20Not AvailableUs
Clonazepamtablet1 mgoralMylan Pharmaceuticals Inc.1998-10-20Not AvailableUs
Clonazepamtablet2 mgoralMylan Pharmaceuticals Inc.1998-10-20Not AvailableUs
Clonazepamtablet, orally disintegrating.125 mgoralBarr Laboratories Inc.2005-08-10Not AvailableUs
Clonazepamtablet, orally disintegrating.25 mgoralBarr Laboratories Inc.2005-08-10Not AvailableUs
Clonazepamtablet, orally disintegrating.5 mgoralBarr Laboratories Inc.2005-08-11Not AvailableUs
Clonazepamtablet, orally disintegrating1 mgoralBarr Laboratories Inc.2005-08-11Not AvailableUs
Clonazepamtablet, orally disintegrating2 mgoralBarr Laboratories Inc.2005-08-11Not AvailableUs
Clonazepamtablet.5 mgoralQualitest Pharmaceuticals2006-06-28Not AvailableUs
Clonazepamtablet1 mgoralQualitest Pharmaceuticals2006-06-28Not AvailableUs
Clonazepamtablet2 mgoralQualitest Pharmaceuticals2006-06-28Not AvailableUs
Clonazepamtablet.5 mgoralUpsher Smith Laboratories, Inc.2014-09-25Not AvailableUs
Clonazepamtablet1 mgoralUpsher Smith Laboratories, Inc.2014-09-25Not AvailableUs
Clonazepamtablet2 mgoralUpsher Smith Laboratories, Inc.2014-09-25Not AvailableUs
Clonazepamtablet.5 mgoralMajor Pharmaceuticals2010-05-14Not AvailableUs
Clonazepamtablet1 mgoralMajor Pharmaceuticals2010-05-14Not AvailableUs
Clonazepamtablet2 mgoralMajor Pharmaceuticals2010-06-17Not AvailableUs
Clonazepamtablet.5 mgoralSTAT Rx USA LLC2009-02-13Not AvailableUs
Clonazepamtablet1 mgoralSTAT Rx USA LLC2009-02-13Not AvailableUs
Clonazepamtablet2 mgoralSTAT Rx USA LLC2009-02-13Not AvailableUs
Clonazepamtablet.5 mgoralAccord Healthcare Inc.2010-11-24Not AvailableUs
Clonazepamtablet1 mgoralAccord Healthcare Inc.2010-11-24Not AvailableUs
Clonazepamtablet2 mgoralAccord Healthcare Inc.2010-11-24Not AvailableUs
Clonazepamtablet.5 mgoralRebel Distributors2009-06-22Not AvailableUs
Clonazepamtablet1 mgoralRebel Distributors2009-06-22Not AvailableUs
Clonazepamtablet2 mgoralRebel Distributors2009-06-22Not AvailableUs
Clonazepamtablet1 mgoralAidarex Pharmaceuticals LLC2006-06-28Not AvailableUs
Clonazepamtablet.5 mgoralAidarex Pharmaceuticals LLC2006-06-28Not AvailableUs
Clonazepamtablet2 mgoralAidarex Pharmaceuticals LLC2006-06-28Not AvailableUs
Clonazepamtablet.5 mgoralLake Erie Medical & Surgical Supply DBA Quality Care Products LLC2009-02-13Not AvailableUs
Clonazepamtablet1 mgoralLake Erie Medical & Surgical Supply DBA Quality Care Products LLC1996-09-17Not AvailableUs
Clonazepamtablet1 mgoralSTAT Rx USA LLC2006-06-28Not AvailableUs
Clonazepamtablet1 mgoralSTAT Rx USA LLC2009-02-13Not AvailableUs
Clonazepamtablet.5 mgoralPd Rx Pharmaceuticals, Inc.1997-08-29Not AvailableUs
Clonazepamtablet1 mgoralAphena Pharma Solutions Tennessee, Llc2006-06-28Not AvailableUs
Clonazepamtablet2 mgoralAphena Pharma Solutions Tennessee, Llc2006-06-28Not AvailableUs
Clonazepamtablet.5 mgoralREMEDYREPACK INC.2010-09-22Not AvailableUs
Clonazepamtablet.5 mgoralREMEDYREPACK INC.2011-06-22Not AvailableUs
Clonazepamtablet, orally disintegrating.125 mgoralPar Pharmaceutical, Inc.2005-08-05Not AvailableUs
Clonazepamtablet, orally disintegrating.25 mgoralPar Pharmaceutical, Inc.2005-08-05Not AvailableUs
Clonazepamtablet, orally disintegrating.5 mgoralPar Pharmaceutical, Inc.2005-08-05Not AvailableUs
Clonazepamtablet, orally disintegrating1 mgoralPar Pharmaceutical, Inc.2005-08-05Not AvailableUs
Clonazepamtablet, orally disintegrating2 mgoralPar Pharmaceutical, Inc.2005-08-05Not AvailableUs
Clonazepamtablet1 mgoralLake Erie Medical & Surgical Supply DBA Quality Care Products LLC2011-12-19Not AvailableUs
Clonazepamtablet.5 mgoralLake Erie Medical & Surgical Supply DBA Quality Care Products LLC2011-12-19Not AvailableUs
Clonazepamtablet1 mgoralA S Medication Solutions Llc2006-06-28Not AvailableUs
Clonazepamtablet.5 mgoralA S Medication Solutions Llc2006-06-28Not AvailableUs
Clonazepamtablet1 mgoralUnit Dose Services2011-12-07Not AvailableUs
Clonazepamtablet.5 mgoralUnit Dose Services2009-02-13Not AvailableUs
Clonazepamtablet1 mgoralUnit Dose Services2011-12-07Not AvailableUs
Clonazepamtablet.5 mgoralMylan Institutional Inc.1997-07-15Not AvailableUs
Clonazepamtablet1 mgoralMylan Institutional Inc.1997-07-15Not AvailableUs
Clonazepamtablet2 mgoralMylan Institutional Inc.1997-07-15Not AvailableUs
Clonazepamtablet1 mgoralNorthwind Pharmaceuticals2014-06-01Not AvailableUs
Clonazepamtablet.5 mgoralREMEDYREPACK INC.2013-02-25Not AvailableUs
Clonazepamtablet1 mgoralREMEDYREPACK INC.2013-02-18Not AvailableUs
Clonazepamtablet1 mgoralREMEDYREPACK INC.2013-12-31Not AvailableUs
Clonazepamtablet2 mgoralREMEDYREPACK INC.2014-06-03Not AvailableUs
Clonazepamtablet1 mgoralREMEDYREPACK INC.2014-06-16Not AvailableUs
Clonazepamtablet.5 mgoralH.J. Harkins Company, Inc.2009-02-13Not AvailableUs
Clonazepamtablet1 mgoralH.J. Harkins Company, Inc.2009-02-13Not AvailableUs
Clonazepamtablet2 mgoralH.J. Harkins Company, Inc.2009-02-13Not AvailableUs
Clonazepamtablet1 mgoralA S Medication Solutions Llc2006-06-28Not AvailableUs
Clonazepamtablet.5 mgoralA S Medication Solutions Llc2006-06-28Not AvailableUs
Clonazepamtablet2 mgoralA S Medication Solutions Llc2006-06-28Not AvailableUs
Clonazepamtablet.5 mgoralPhysicians Total Care, Inc.2005-05-16Not AvailableUs
Clonazepamtablet1 mgoralPhysicians Total Care, Inc.2003-09-25Not AvailableUs
Clonazepamtablet2 mgoralPhysicians Total Care, Inc.2009-06-26Not AvailableUs
Clonazepamtablet, orally disintegrating.25 mgoralPhysicians Total Care, Inc.2011-01-14Not AvailableUs
Clonazepamtablet.5 mgoralCardinal Health1997-08-29Not AvailableUs
Clonazepamtablet.5 mgoralCardinal Health2009-12-31Not AvailableUs
Clonazepamtablet1 mgoralCardinal Health2009-12-31Not AvailableUs
Clonazepamtablet.5 mgoralCardinal Health2009-02-13Not AvailableUs
Clonazepamtablet1 mgoralCardinal Health2009-02-13Not AvailableUs
Clonazepamtablet2 mgoralCardinal Health2009-02-13Not AvailableUs
Clonazepamtablet.5 mgoralCardinal Health2007-08-01Not AvailableUs
Clonazepamtablet2 mgoralPd Rx Pharmaceuticals, Inc.1997-08-29Not AvailableUs
Clonazepamtablet1 mgoralPd Rx Pharmaceuticals, Inc.1997-08-29Not AvailableUs
Clonazepamtablet.5 mgoralPd Rx Pharmaceuticals, Inc.2006-06-28Not AvailableUs
Clonazepamtablet.5 mgoralCaraco Pharmaceutical Laboratories, Ltd.2001-08-31Not AvailableUs
Clonazepamtablet1 mgoralCaraco Pharmaceutical Laboratories, Ltd.2001-08-31Not AvailableUs
Clonazepamtablet2 mgoralCaraco Pharmaceutical Laboratories, Ltd.2001-08-31Not AvailableUs
Clonazepamtablet.5 mgoralGolden State Medical Supply, Inc.2013-10-18Not AvailableUs
Clonazepamtablet1 mgoralGolden State Medical Supply, Inc.2013-10-18Not AvailableUs
Clonazepamtablet2 mgoralGolden State Medical Supply, Inc.2013-10-18Not AvailableUs
Clonazepamtablet2 mgoralREMEDYREPACK INC.2015-02-13Not AvailableUs
Clonazepamtablet.5 mgoralDIRECT RX2014-01-01Not AvailableUs
Clonazepamtablet1 mgoralDIRECT RX2014-01-01Not AvailableUs
Clonazepamtablet2 mgoralDIRECT RX2014-01-01Not AvailableUs
Clonazepamtablet.5 mgoralProficient Rx LP1996-09-18Not AvailableUs
Clonazepamtablet1 mgoralbryant ranch prepack2006-06-28Not AvailableUs
Clonazepamtablet.5 mgoralbryant ranch prepack2006-06-28Not AvailableUs
Clonazepamtablet2 mgoralbryant ranch prepack2006-06-28Not AvailableUs
Clonazepamtablet.5 mgoralMc Kesson Packaging Services Business Unit Of Mc Kesson Corporation2007-08-01Not AvailableUs
Clonazepamtablet1 mgoralMc Kesson Packaging Services Business Unit Of Mc Kesson Corporation2007-08-02Not AvailableUs
Clonazepamtablet.5 mgoralTYA Pharmaceuticals2010-11-24Not AvailableUs
Clonazepamtablet1 mgoralTYA Pharmaceuticals2009-02-13Not AvailableUs
Clonazepamtablet2 mgoralTYA Pharmaceuticals2009-02-13Not AvailableUs
Clonazepamtablet1 mgoralDispensing Solutions, Inc.2006-06-28Not AvailableUs
Clonazepamtablet2 mgoralDispensing Solutions, Inc.2006-06-28Not AvailableUs
Clonazepamtablet.5 mgoralDispensing Solutions, Inc.2006-06-28Not AvailableUs
Clonazepamtablet.5 mgoralContract Pharmacy Services Pa2010-07-01Not AvailableUs
Clonazepamtablet1 mgoralContract Pharmacy Services Pa2010-07-01Not AvailableUs
Clonazepamtablet2 mgoralContract Pharmacy Services Pa2010-07-01Not AvailableUs
Clonazepamtablet1 mgoralAphena Pharma Solutions Tennessee, Llc2009-02-13Not AvailableUs
Clonazepamtablet.5 mgoralAphena Pharma Solutions Tennessee, Llc2009-02-13Not AvailableUs
Clonazepamtablet2 mgoralAphena Pharma Solutions Tennessee, Llc2009-02-13Not AvailableUs
Clonazepamtablet.5 mgoralAphena Pharma Solutions Tennessee, Llc2006-06-28Not AvailableUs
Clonazepamtablet2 mgoralPreferred Pharmaceuticals, Inc.2014-07-28Not AvailableUs
Clonazepamtablet.5 mgoralPreferred Pharmaceuticals, Inc.2014-07-28Not AvailableUs
Clonazepamtablet1 mgoralPreferred Pharmaceuticals, Inc.2014-04-02Not AvailableUs
Clonazepamtablet1 mgoralPreferred Pharmaceuticals, Inc.2012-01-17Not AvailableUs
Clonazepamtablet.5 mgoralPreferred Pharmaceuticals, Inc.2012-01-17Not AvailableUs
Clonazepamtablet.5 mgoralMc Kesson Contract Packaging2011-10-11Not AvailableUs
Clonazepamtablet1 mgoralMc Kesson Contract Packaging2011-10-12Not AvailableUs
Clonazepamtablet2 mgoralMc Kesson Contract Packaging2011-10-18Not AvailableUs
Over the Counter ProductsNot Available
International Brands
NameCompany
AntelepsinAWD
IktorivilRoche
RivotrilRoche
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number1622-61-3
WeightAverage: 315.711
Monoisotopic: 315.041068908
Chemical FormulaC15H10ClN3O3
InChI KeyDGBIGWXXNGSACT-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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzodiazepines
Sub Class1,4-benzodiazepines
Direct Parent1,4-benzodiazepines
Alternative Parents
Substituents
  • 1,4-benzodiazepine
  • Halobenzene
  • Chlorobenzene
  • Benzenoid
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl chloride
  • Organic nitro compound
  • Secondary carboxylic acid amide
  • Organic nitrite
  • C-nitro compound
  • Lactam
  • Ketimine
  • Carboxamide group
  • Azacycle
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Allyl-type 1,3-dipolar organic compound
  • Organic oxoazanium
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organic salt
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Imine
  • Carbonyl group
  • Organic zwitterion
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationClonazepam 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.
PharmacodynamicsClonazepam, 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 actionAllosteric 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.
AbsorptionClonazepam is rapidly and completely absorbed after oral administration. The absolute bioavailability of clonazepam is about 90%. Cmax, oral administration = 1 -4 hours.
Volume of distributionNot Available
Protein binding85% 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 eliminationClonazepam 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 life30-40 hours
ClearanceNot Available
ToxicitySomnolence, 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 substrateInhibitor0.5213
CYP450 2D6 substrateNon-inhibitor0.8271
CYP450 2C19 substrateInhibitor0.7441
CYP450 3A4 substrateInhibitor0.5565
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
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Tabletoral.5 mg
Tabletoral1 mg
Tabletoral2 mg
Tablet, orally disintegratingoral.125 mg
Tablet, orally disintegratingoral.25 mg
Tablet, orally disintegratingoral.5 mg
Tablet, orally disintegratingoral1 mg
Tablet, orally disintegratingoral2 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.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point238-240Kariss, 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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraMS
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 Reference
  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
  2. Robertson MD, Drummer OH: Postmortem drug metabolism by bacteria. J Forensic Sci. 1995 May;40(3):382-6. Pubmed
  3. Rosen GM, Turner MJ 3rd: Synthesis of spin traps specific for hydroxyl radical. J Med Chem. 1988 Feb;31(2):428-32. Pubmed
  4. Rosen GM, Demos HA, Rauckman EJ: Not all aromatic nitro compounds form free radicals. Toxicol Lett. 1984 Aug;22(2):145-52. Pubmed
  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
External Links
ATC CodesN03AE01
AHFS Codes
  • 28:12.08
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (74.3 KB)
Interactions
Drug Interactions
Drug
CimetidineCimetidine may increase the effect of the benzodiazepine, clonazepam.
ClozapineIncreased risk of toxicity
FluconazoleFluconazole may increase the effect of the benzodiazepine, clonazepam.
IndinavirThe protease inhibitor, indinavir, may increase the effect of the benzodiazepine, clonazepam.
ItraconazoleItraconazole may increase the effect of the benzodiazepine, clonazepam.
KavaKava may increase the effect of the benzodiazepine, clonazepam.
KetoconazoleKetoconazole may increase the effect of the benzodiazepine, clonazepam.
NelfinavirThe protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, clonazepam.
OmeprazoleOmeprazole may increase the effect of the benzodiazepine, clonazepam.
RitonavirThe protease inhibitor, ritonavir, may increase the effect of the benzodiazepine, clonazepam.
SaquinavirThe protease inhibitor, saquinavir, may increase the effect of the benzodiazepine, clonazepam.
St. John's WortSt. John's Wort may decrease the effect of the benzodiazepine, clonazepam.
TelithromycinTelithromycin may reduce clearance of Clonazepam. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Clonazepam if Telithromycin is initiated, discontinued or dose changed.
TipranavirTipranavir may decrease the metabolism and clearance of Clonazepam. Consider alternate therapy or monitor for Clonazepam toxic effects if Tipranavir is initiated or dose increased.
TriprolidineThe CNS depressants, Triprolidine and Clonazepam, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
VigabatrinVigabatrin increases Cmax of clonazepam by 30% and decreases Tmax by 45%
VoriconazoleVoriconazole may increase the serum concentration of clonazepam by decreasing its metabolism. Monitor for clonazepam toxicity if voriconazole is initiated or dose increased.
Food Interactions
  • Avoid alcohol.
  • Avoid excessive quantities of coffee or tea (Caffeine).
  • Take without regard to meals.

Targets

1. GABA-A receptor (anion channel)

Kind: protein group

Organism: Human

Pharmacological action: yes

Actions: positive allosteric modulator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit alpha-1 P14867 Details
Gamma-aminobutyric acid receptor subunit alpha-2 P47869 Details
Gamma-aminobutyric acid receptor subunit alpha-3 P34903 Details
Gamma-aminobutyric acid receptor subunit alpha-4 P48169 Details
Gamma-aminobutyric acid receptor subunit alpha-5 P31644 Details
Gamma-aminobutyric acid receptor subunit alpha-6 Q16445 Details
Gamma-aminobutyric acid receptor subunit beta-1 P18505 Details
Gamma-aminobutyric acid receptor subunit beta-2 P47870 Details
Gamma-aminobutyric acid receptor subunit beta-3 P28472 Details
Gamma-aminobutyric acid receptor subunit delta O14764 Details
Gamma-aminobutyric acid receptor subunit epsilon P78334 Details
Gamma-aminobutyric acid receptor subunit gamma-1 Q8N1C3 Details
Gamma-aminobutyric acid receptor subunit gamma-2 P18507 Details
Gamma-aminobutyric acid receptor subunit gamma-3 Q99928 Details
Gamma-aminobutyric acid receptor subunit pi O00591 Details
Gamma-aminobutyric acid receptor subunit theta Q9UN88 Details

References:

  1. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. Pubmed
  2. Riss J, Cloyd J, Gates J, Collins S: Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008 Aug;118(2):69-86. Epub 2008 Mar 31. Pubmed

2. Translocator protein

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: other/unknown

Components

Name UniProt ID Details
Translocator protein P30536 Details

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
  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
  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
  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
  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
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2E1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2E1 P05181 Details

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

3. Arylamine N-acetyltransferase 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Arylamine N-acetyltransferase 2 P11245 Details

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
  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

Carriers

1. Serum albumin

Kind: protein

Organism: Human

Pharmacological action: no

Components

Name UniProt ID Details
Serum albumin P02768 Details

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

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Drug created on June 13, 2005 07:24 / Updated on April 08, 2014 11:18