Identification

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

A benzodiazepine used to treat various seizures, including myotonic or atonic seizures, photosensitive epilepsy, and absence seizures, although tolerance may develop Label 11,12,13,14. The agent has also been indicated for treating panic disorder Label 7,11,12,13,14. The mechanism of action appears to involve the enhancement of gamma-aminobutyric acid receptor responses Label 7,8,11,12,13,14.

Since being first patented in 1960 and then released for sale from Roche in the US in 1975 9,10, clonazepam has experienced a storied history in the treatment of the aforementioned medical conditions. Now available as a generic medication, the agent continues to see exceptionally high use as millions of prescriptions are written for the medication internationally every year. Unfortunately, however, like most benzodiazepines, clonazepam use has also been associated with recreational use and drug abuse Label 11,12,13,14.

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
ClonapamTabletOralValeant Canada Lp Valeant Canada S.E.C.1997-02-28Not applicableCanada
ClonapamTabletOralValeant Canada Lp Valeant Canada S.E.C.1997-01-31Not applicableCanada
ClonapamTabletOralValeant Canada Lp Valeant Canada S.E.C.1997-01-31Not applicableCanada
ClonazepamTablet1 mg/1OralVintage Pharmaceuticals, LLC2006-10-182006-10-18Us
ClonazepamTablet0.25 mgOralSivem Pharmaceuticals Ulc2015-07-092017-07-12Canada
ClonazepamTablet1 mgOralMeliapharm Inc2010-10-202014-06-25Canada
ClonazepamTablet2 mg/1OralWatson Pharmaceuticals2008-03-18Not applicableUs
ClonazepamTablet0.5 mg/1OralVintage Pharmaceuticals, LLC2006-10-182006-10-18Us
ClonazepamTablet1 mgOralSivem Pharmaceuticals Ulc2015-07-092017-12-19Canada
ClonazepamTablet1 mg/1OralWatson Pharmaceuticals2008-03-18Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Accel-clonazepamTabletOralAccel Pharma IncNot applicableNot applicableCanada
Accel-clonazepamTabletOralAccel Pharma IncNot applicableNot applicableCanada
Accel-clonazepamTabletOralAccel Pharma IncNot applicableNot applicableCanada
Apo-clonazepam - Tab 0.5mgTabletOralApotex Corporation1995-12-31Not applicableCanada
Apo-clonazepam - Tab 2mgTabletOralApotex Corporation1995-12-31Not applicableCanada
ClonazepamTablet0.5 mg/1OralCaremark L.L.C.2009-05-112012-05-31Us
ClonazepamTablet1 mg/1OralDispensing Solutions, Inc.2006-06-28Not applicableUs
ClonazepamTablet0.5 mg/1OralTYA Pharmaceuticals2010-11-24Not applicableUs
ClonazepamTablet, orally disintegrating0.125 mg/1OralPar Pharmaceutical2005-08-05Not applicableUs
ClonazepamTablet1 mg/1OralUpsher Smith Laboratories2014-09-252017-08-31Us
Additional Data Available
  • Application Number
    Application Number

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  • Product Code
    Product Code

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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 indicated as monotherapy or as an adjunct in the treatment of Lennox-Gastaut syndrome (petit mal variant), akinetic, and myoclonic seizures Label 13. Furthermore, clonazepam may also be of some value in patients with absence spells (petit mal) who have failed to respond to succinimides Label 13. Additionally, clonazepam is also indicated for the treatment of panic disorder, with or without agoraphobia, as defined in the DSM-V Label.

Alternatively, some regional prescribing information note that clonazepam is indicated for all clinical forms of epileptic disease and seizures in adults, especially absence seizures (petit mal) including atypical absence; primary or secondarily generalised tonic-clonic (grand mal), tonic or clonic seizures; partial (focal) seizures with elementary or complex symptomatology; various forms of myoclonic seizures, myoclonus and associated abnormal movements 11,14. Such regional label data also has clonazepam indicated for most types of epilepsy in infants and children, especially absences (petit mal), myoclonic seizures and tonic-clonic fits, whether due to primary generalized epilepsy or to secondary generalization of partial epilepsy 14.

Associated Conditions
Pharmacodynamics

The pharmacodynamic properties of clonazepam are common among benzodiazepines and include anticonvulsive, sedative, muscle relaxing and anxiolytic effects 6,11,12,13. Animal data and electroencephalographic investigations in man have shown that clonazepam rapidly suppresses many types of paroxysmal activity including the spike and wave discharge in absence seizures (petit mal), slow spike wave, generalized spike wave, spikes with temporal or other locations, as well as irregular spikes and waves Label 6,11,12,13. Moreover, the agent can also decrease the frequency, amplitude, duration, and spread of discharge in minor motor seizures Label 12.

Generalized EEG abnormalities are more readily suppressed by clonazepam than are focal EEG abnormalities such as focal spikes 11. Clonazepam has beneficial effects in generalized and focal epilepsies 11.

Mechanism of action

Gamma-Aminobutyric acid (GABA) is considered the principal inhibitory neurotransmitter in the human body 6,7,8. When GABA binds to GABA(a) receptors found in neuron synapses, chloride ions are conducted across neuron cell membranes via an ion channel in the receptors 6,7,8,13. With enough chloride ions conducted, the local, associated neuron membrane potentials are hyperpolarized - making it more difficult or less likely for action potentials to fire, ultimately resulting in less excitation of the neurons 6,7,8,13.

Subsequently, benzodiazepines like clonazepam can bind to benzodiazepine receptors that are components of various varieties of GABA(a) receptors 6,7,8,13,11,12. This binding acts to enhance the effects of GABA by increasing GABA affinity for the GABA(a) receptor, which ultimately enhances GABA ligand binding at the receptors 6,7,8,13,11,12. This enhanced ligand binding of the inhibitory neurotransmitter GABA to the receptors increases the aforementioned chloride ion conduction (perhaps reportedly via an increase in the frequency of the chloride channel opening), resulting in a hyperpolarized cell membrane that prevents further excitation of the associated neuron cells 6,7,8,13,11,12. Combined with the notion that such benzodiazepine receptor associated GABA(a) receptors exist both peripherally and in the CNS, this activity consequently facilitates various effects like sedation, hypnosis, skeletal muscle relaxation, anticonvulsant activity, and anxiolytic action 6,7,8,13,11,12.

In particular, when out of the ordinary rapid and repetitive electrical signals are released in the CNS, it is proposed that the brain can become over-stimulated and ordinary functions are disrupted - resulting in seizure activity 8. By enhancing the neuro-inhibitory activity of GABA, it is believed that clonazepam can facilitate in decreasing any excessive electrical nerve activity in the CNS that might be contributing to seizures 8. Concurrently, it is also believed that clonazepam's actions in enhancing GABA effects may inhibit neuronal activity proposed to occur in amygdala-centered fear circuits - therefore assisting in the management of anxiety or panic 7.

TargetActionsOrganism
AGABA-A receptor (anion channel)
positive allosteric modulator
Humans
UTranslocator protein
other/unknown
Humans
UNuclear receptor subfamily 1 group I member 2
partial agonist
Humans
Additional Data Available
Adverse Effects

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Additional Data Available
Contraindications

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Additional Data Available
Blackbox Warnings

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Absorption

Clonazepam is rapidly and almost entirely absorbed after oral administration as tablets Label 12,14. Peak plasma concentrations of clonazepam administered by the oral route are reached within 1-4 hours and the associated absorption half-life is about 25 minutes Label 12,14. The absolute bioavailability is approximately 90% - but with substantially large differences between individuals Label 12,14.

Volume of distribution

Clonazepam distributes very rapidly to various organs and body tissues with preferential uptake by brain structures 12,14. The apparent volume of distribution has been documented as approximately 3 L/kg 12,14.

Protein binding

The recorded plasma protein binding of clonazepam ranges between 82–86% 12,14.

Metabolism

Clonazepam is metabolized principally in the liver 12,14. The metabolic pathways include hydroxylation, reduction of the nitro groups to amine groups, and the addition of acetate to the amino grouping 12,14. In particular, clonazepam is extensively metabolized by reduction to 7-amino-clonazepam and by N-acetylation to 7-acetamido-clonazepam 12,14. Hydroxylation at the C-3 position also occurs 12,14. Hepatic cytochrome P450 3A4 is implicated in the nitroreduction of clonazepam to pharmacologically inactive metabolites 12,14.

Route of elimination

Approximately 50-70% of a clonazepam dose is excreted in the urine and 10-30% is excreted in the feces as metabolites 12,14. The excretion of unchanged clonazepam in the urine is typically less than 2% of the administered dose 12,14. Metabolites of clonazepam are present in urine as both free and conjugated (glucuronide and sulfate) compounds 12,14.

Half life

The mean elimination half-life determined for clonazepam is independent of the dose given and has been documented as being about 30-40 hours 12,14.

Clearance

The documented clearance for clonazepam is approximately 55 ml/min regardless of gender 12. Nevertheless, clearance values normalized by weight decline with increasing body weight 12.

Toxicity

Benzodiazepines like clonazepam commonly cause drowsiness, ataxia, dysarthria, and nystagmus. Overdose with clonazepam is generally not life-threatening if the drug is taken alone, but may lead to areflexia, apnea, hypotension, cardiorespiratory depression, and coma. Coma, if it does occur, usually lasts a few hours but it can become more protracted and cyclical, especially in elderly patients. Increased frequency of seizures may occur in patients at supratherapeutic plasma concentrations. Benzodiazepine respiratory depressant effects are more serious when compounded in patients with respiratory disease.

An increased risk of congenital malformations associated with the use of benzodiazepine drugs like clonazepam has been suggested in several studies Label 12,14. There may also be non-teratogenic risks associated with the use of benzodiazepines during pregnancy Label 12,14. There have been reports of neonatal flaccidity, respiratory and feeding difficulties, and hypothermia in children born to mothers who have been receiving benzodiazepines late in pregnancy Label 12,14. In addition, children born to mothers receiving benzodiazepines late in pregnancy may be at some risk of experiencing withdrawal symptoms during the postnatal period Label 12,14. In general, it is best for patients who are of childbearing potential and also use benzodiazepines like clonazepam to discuss such matters with their health care professionals as careful consideration must be undertaken regarding the intersection of the risks of untreated seizure potential in the patient and any possible toxicity to the fetus Label 12,14.

Although the active ingredient of clonazepam has been found to pass into the maternal milk in small amounts only, mothers receiving clonazepam should not breast-feed their infants Label 12,14.

Since the possibility that adverse effects on the physical or mental development of the child could become apparent only after a number of years, the risk-benefit consideration of the long-term use of clonazepam in pediatric patients younger than five years of age is important Label 12,14.

The pharmacological effects of benzodiazepines like clonazepam appear to be greater in elderly patients than in younger patients even at similar plasma benzodiazepine concentrations, possibly because of age-related changes in drug-receptor interactions, post-receptor mechanisms, and organ function Label 12,14. In general elderly patients should be started on the lowest possible dose of clonazepam and observed closely Label 12,14. There is an increased risk for falls and fractures among elderly and debilitated benzodiazepine users Label 12,14. The risk is increased in those taking concomitant sedatives, including substances like benzodiazepines, alcoholic beverages, and so on Label 12,14.

Some oral LD50 values documented are >4000 mg/kg for the mouse model, >4000 mg/kg for the adult rat model, and >2000 mg/kg for the rabbit model 12.

Affected organisms
  • Humans and other mammals
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
(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.
3,5-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.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Clonazepam is combined with 5-methoxy-N,N-dimethyltryptamine.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

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  • Action
    Action

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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]
  6. DeVane CL, Ware MR, Lydiard RB: Pharmacokinetics, pharmacodynamics, and treatment issues of benzodiazepines: alprazolam, adinazolam, and clonazepam. Psychopharmacol Bull. 1991;27(4):463-73. [PubMed:1687613]
  7. Nardi AE, Machado S, Almada LF, Paes F, Silva AC, Marques RJ, Amrein R, Freire RC, Martin-Santos R, Cosci F, Hallak JE, Crippa JA, Arias-Carrion O: Clonazepam for the treatment of panic disorder. Curr Drug Targets. 2013 Mar;14(3):353-64. [PubMed:23256724]
  8. Jenner P, Pratt JA, Marsden CD: Mechanism of action of clonazepam in myoclonus in relation to effects on GABA and 5-HT. Adv Neurol. 1986;43:629-43. [PubMed:2418652]
  9. Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. [ISBN:9783527607495]
  10. Shorter, Edward (2005). A Historical Dictionary of Psychiatry. Oxford University Press. [ISBN:9780190292010]
  11. Electronic Medicines Compendium: Clonazepam Rosemont 2mg/5ml Oral Solution [Link]
  12. Rivotril (Clonazepam) 0.5 mg and 2 mg Tablets Canadian Product Monograph [File]
  13. Clonazepam Fact Sheet from http://cdn.neiglobal.com/content/pg/live/clonazepam.pdf [File]
  14. Rivotril (Clonazepam) Australian Product Information [File]
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
FDA label
Download (513 KB)
MSDS
Download (74.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedTreatmentBurning Mouth Syndrome1
1CompletedNot AvailablePharmacokinetics1
1CompletedNot AvailableTo Determine Bioequivalence Under Fasting Conditions2
1CompletedTreatmentPain, 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
TabletOral0.25 mg
TabletOral0.5 mg
TabletOral0.5 mg/1
TabletOral1 mg
TabletOral1 mg/1
TabletOral2 mg/1
TabletOral2 mg
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
TabletOral
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
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. 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
Humans
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
Humans
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
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. Seree EJ, Pisano PJ, Placidi M, Rahmani R, Barra YA: Identification of the human and animal hepatic cytochromes P450 involved in clonazepam metabolism. Fundam Clin Pharmacol. 1993;7(2):69-75. [PubMed:8486332]
Kind
Protein
Organism
Humans
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. doi: 10.1080/004982598239579 . [PubMed:9574817]
Kind
Protein
Organism
Humans
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
Humans
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 September 13, 2019 09:27