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Details

Stereochemistry ACHIRAL
Molecular Formula C15H10ClN3O3.ClH
Molecular Weight 352.172
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CLONAZEPAM HYDROCHLORIDE

SMILES

Cl.[O-][N+](=O)C1=CC=C2NC(=O)CN=C(C3=CC=CC=C3Cl)C2=C1

InChI

InChIKey=VWRNQDQMIQNCOC-UHFFFAOYSA-N
InChI=1S/C15H10ClN3O3.ClH/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);1H

HIDE SMILES / InChI
Molecular Formula C15H10ClN3O3
Molecular Weight 315.711
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

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. Klonopin is the brand name for Clonazepam, an anxiolytic and anticonvulsant. The precise mechanism by which clonazepam exerts its antiseizure and antipanic effects is unknown, although it is believed to be related to its ability to enhance the activity of gamma aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. 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.

CNS Activity

Originator

Approval Year

1975
63
Targets

Targets

Primary TargetPharmacologyConditionPotency
Agonist
2752
 0.06 nM [EC50]
Agonist
2752
 57.0 µM [EC50]
Agonist
2752
 40.0 µM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8583
KLONOPIN

Approved Use

INDICATIONS & USAGE Seizure Disorders: Clonazepam tablets, USP are useful alone or as an adjunct in the treatment of the Lennox-Gastaut syndrome (petit mal variant), akinetic and . In patients with absence seizures (petit mal) who have failed to respond to succinimides, clonazepam may be useful. In some studies, up to 30% of patients have shown a loss of anticonvulsant activity, often within 3 months of administration. In some cases, dosage adjustment may reestablish efficacy. Panic Disorder: Clonazepam tablets, USP are indicated for the treatment of panic disorder, with or without agoraphobia, as defined in DSM-IV. Panic disorder is characterized by the occurrence of unexpected panic attacks and associated concern about having additional attacks, worry about the implications or consequences of the attacks, and/or a significant change in behavior related to the attacks. The efficacy of clonazepam was established in two 6- to 9-week trials in panic disorder patients whose diagnoses corresponded to the DSM-IIIR category of panic disorder. Panic disorder (DSM-IV) is characterized by recurrent unexpected panic attacks, ie, a discrete period of intense fear or discomfort in which four (or more) of the following symptoms develop abruptly and reach a peak within 10 minutes: (1) palpitations, pounding heart or accelerated heart rate; (2) sweating; (3) trembling or shaking; (4) sensations of shortness of breath or smothering; (5) feeling of choking; (6) chest pain or discomfort; (7) nausea or abdominal distress; (8) feeling dizzy, unsteady, lightheaded or faint; (9) derealization (feelings of unreality) or depersonalization (being detached from oneself); (10) fear of losing control; (11) fear of dying; (12) paresthesias (numbness or tingling sensations); (13) chills or hot flushes. The effectiveness of clonazepam in long-term use, that is, for more than 9 weeks, has not been systematically studied in controlled clinical trials. The physician who elects to use clonazepam for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.

Launch Date

1975
Primary
Approved
8583
KLONOPIN

Approved Use

INDICATIONS & USAGE Seizure Disorders: Clonazepam tablets, USP are useful alone or as an adjunct in the treatment of the Lennox-Gastaut syndrome (petit mal variant), akinetic and . In patients with absence seizures (petit mal) who have failed to respond to succinimides, clonazepam may be useful. In some studies, up to 30% of patients have shown a loss of anticonvulsant activity, often within 3 months of administration. In some cases, dosage adjustment may reestablish efficacy. Panic Disorder: Clonazepam tablets, USP are indicated for the treatment of panic disorder, with or without agoraphobia, as defined in DSM-IV. Panic disorder is characterized by the occurrence of unexpected panic attacks and associated concern about having additional attacks, worry about the implications or consequences of the attacks, and/or a significant change in behavior related to the attacks. The efficacy of clonazepam was established in two 6- to 9-week trials in panic disorder patients whose diagnoses corresponded to the DSM-IIIR category of panic disorder. Panic disorder (DSM-IV) is characterized by recurrent unexpected panic attacks, ie, a discrete period of intense fear or discomfort in which four (or more) of the following symptoms develop abruptly and reach a peak within 10 minutes: (1) palpitations, pounding heart or accelerated heart rate; (2) sweating; (3) trembling or shaking; (4) sensations of shortness of breath or smothering; (5) feeling of choking; (6) chest pain or discomfort; (7) nausea or abdominal distress; (8) feeling dizzy, unsteady, lightheaded or faint; (9) derealization (feelings of unreality) or depersonalization (being detached from oneself); (10) fear of losing control; (11) fear of dying; (12) paresthesias (numbness or tingling sensations); (13) chills or hot flushes. The effectiveness of clonazepam in long-term use, that is, for more than 9 weeks, has not been systematically studied in controlled clinical trials. The physician who elects to use clonazepam for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.

Launch Date

1975
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2.3 ng/mL
EXPERIMENT
https://accp1.onlinelibrary.wiley.com/doi/epdf/10.1177/0091270005280861
0.5 mg single, oral
dose: 0.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CLONAZEPAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
3 ng/mL
REVIEW
https://accp1.onlinelibrary.wiley.com/doi/epdf/10.1177/0091270005280861
0.5 mg 3 times / day steady-state, oral
dose: 0.5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CLONAZEPAM plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
102 ng × h/mL
EXPERIMENT
https://accp1.onlinelibrary.wiley.com/doi/epdf/10.1177/0091270005280861
0.5 mg single, oral
dose: 0.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CLONAZEPAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
339 ng × h/mL
REVIEW
https://accp1.onlinelibrary.wiley.com/doi/epdf/10.1177/0091270005280861
0.5 mg 3 times / day steady-state, oral
dose: 0.5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CLONAZEPAM plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
40 h
REVIEW
https://accp1.onlinelibrary.wiley.com/doi/epdf/10.1177/0091270005280861
0.5 mg 3 times / day steady-state, oral
dose: 0.5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CLONAZEPAM plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
15%
EXPERIMENT
https://accp1.onlinelibrary.wiley.com/doi/epdf/10.1177/0091270005280861
0.5 mg single, oral
dose: 0.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CLONAZEPAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
2 mg single, intramuscular
Dose: 2 mg
Route: intramuscular
Route: single
Dose: 2 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/12646763
healthy, 30 years (range: 23–50 years)
Health Status: healthy
Age Group: 30 years (range: 23–50 years)
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/12646763
Sources:
https://pubmed.ncbi.nlm.nih.gov/12646763
2 mg single, intravenous
Dose: 2 mg
Route: intravenous
Route: single
Dose: 2 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/12646763
healthy, 30 years (range: 23–50 years)
Health Status: healthy
Age Group: 30 years (range: 23–50 years)
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/12646763
Sources:
https://pubmed.ncbi.nlm.nih.gov/12646763
2 mg single, oral
Dose: 2 mg
Route: oral
Route: single
Dose: 2 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/12646763
healthy, 30 years (range: 23–50 years)
Health Status: healthy
Age Group: 30 years (range: 23–50 years)
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/12646763
Sources:
https://pubmed.ncbi.nlm.nih.gov/12646763
1.5 mg 1 times / day multiple, oral
Recommended
Dose: 1.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1.5 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020813s010lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020813s010lbl.pdf
Disc. AE: Somnolence, Depression...
AEs leading to
discontinuation/dose reduction:
Somnolence (7%)
Depression (4%)
Nervousness (1%)
Dizziness (1%)
Ataxia (1%)
Intellectual disability (1%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020813s010lbl.pdf
6 mg 1 times / day steady, oral
Studied dose
Dose: 6 mg, 1 times / day
Route: oral
Route: steady
Dose: 6 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/3279721
unhealthy
Health Status: unhealthy
Sources:
https://pubmed.ncbi.nlm.nih.gov/3279721
Sources:
https://pubmed.ncbi.nlm.nih.gov/3279721
AEs

AEs

AESignificanceDosePopulation
Ataxia 1%
Disc. AE
1.5 mg 1 times / day multiple, oral
Recommended
Dose: 1.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1.5 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020813s010lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020813s010lbl.pdf
Dizziness 1%
Disc. AE
1.5 mg 1 times / day multiple, oral
Recommended
Dose: 1.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1.5 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020813s010lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020813s010lbl.pdf
Intellectual disability 1%
Disc. AE
1.5 mg 1 times / day multiple, oral
Recommended
Dose: 1.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1.5 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020813s010lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020813s010lbl.pdf
Nervousness 1%
Disc. AE
1.5 mg 1 times / day multiple, oral
Recommended
Dose: 1.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1.5 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020813s010lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020813s010lbl.pdf
Depression 4%
Disc. AE
1.5 mg 1 times / day multiple, oral
Recommended
Dose: 1.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1.5 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020813s010lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020813s010lbl.pdf
Somnolence 7%
Disc. AE
1.5 mg 1 times / day multiple, oral
Recommended
Dose: 1.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1.5 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020813s010lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020813s010lbl.pdf
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1946

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP2B6
926

CYP2E1
1060

UGT
45
CYP3A
220

BCRP
697
CYP
74

UGT
32
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP
150
 no
UGT
70
 no
UGT
70
 no
CYP2B6
1160
 weak
CYP2E1
1146
 yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
BCRP
697
 no
CYP3A
220
 yes
CYP3A4
1946
 yes
yes (pharmacogenomic study)
Comment: The statistical analysis displayed significant association between the patients’ CYP3A4 expression and the stable plasma concentrations of clonazepam normalized by the dose and the patient’s bodyweight.
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:3756
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3756
eMolecules
535779
https://www.emolecules.com/cgi-bin/more?vid=535779
ZINC
ZINC000003813003
http://zinc15.docking.org/substances/ZINC000003813003
PubMed

PubMed

TitleDatePubMed
Interaction of GYKI 52466, a selective non-competitive antagonist of AMPA/kainate receptors, with conventional antiepileptic drugs in amygdala-kindled seizures in rats.
2002-01-15
Spectrofluorimetric determination of vigabatrin and gabapentin in urine and dosage forms through derivatization with fluorescamine.
2002-01-01
Effects of commonly used benzodiazepines on the fetus, the neonate, and the nursing infant.
2002-01
Roles for mitochondrial and reverse mode Na+/Ca2+ exchange and the plasmalemma Ca2+ ATPase in post-tetanic potentiation at crayfish neuromuscular junctions.
2001-12-15
Pharmacoepidemiologic investigation of a clonazepam-carbamazepine interaction by mixed effect modeling using routine clinical pharmacokinetic data in Japanese patients.
2001-12
Pharmacological characterization of the 6 Hz psychomotor seizure model of partial epilepsy.
2001-12
Direct LC analysis of five benzodiazepines in human urine and plasma using an ADS restricted access extraction column.
2001-12
Determination of benzodiazepines in human hair by on-line high-performance liquid chromatography using a restricted access extraction column.
2001-11-15
[Piracetam in the treatment of a patient with idiopathic cortical myoclonus].
2001-11-10
Stiff leg syndrome: case report.
2001-11
Fast orthostatic tremor in Parkinson's disease mimicking primary orthostatic tremor.
2001-11
Selective, high-resolution fluorescence imaging of mitochondrial Ca2+ concentration.
2001-11
West syndrome: the Philippine experience.
2001-11
Kinetic and pharmacological properties of GABA(A) receptors in single thalamic neurons and GABA(A) subunit expression.
2001-11
Increased [Mg2+]o reduces Ca2+ influx and disruption of mitochondrial membrane potential during reoxygenation.
2001-11
Successful use of methadone in the treatment of chronic neuropathic pain arising from burn injuries: a case-study.
2001-11
Nutritional parameters modify muricidal behavior of male Wistar rats: preventive effects of amino acids and 4' Cl diazepam.
2001-10-26
Evaluation of in vitro percutaneous absorption of lorazepam and clonazepam from hydro-alcoholic gel formulations.
2001-10-09
Population pharmacokinetic analysis resulting in a tool for dose individualization of busulphan in bone marrow transplantation recipients.
2001-10
Influence of age and comedication on steady-state clonazepam serum level-dose ratios in Japanese epileptic patients.
2001-10
Diazepam inhibits HIV-1 Tat-induced migration of human microglia.
2001-10
2-Arylpyrazolo[1,5-a]pyrimidin-3-yl acetamides. New potent and selective peripheral benzodiazepine receptor ligands.
2001-10
Effect of clonazepam treatment on antipsychotic drug-induced Meige syndrome and changes in plasma levels of GABA, HVA, and MHPG during treatment.
2001-10
A successful clonazepam treatment without tolerance in a patient with spontaneous oral dyskinesia.
2001-10
[Treatment and long-term follow-up of post-anoxic myoclonus].
2001-09-23
Effect of midazolam on interleukin-6 mRNA expression in human peripheral blood mononuclear cells in the absence of lipopolysaccharide.
2001-09-21
Evaluation of polymeric nanoparticles composed of cholic acid and methoxy poly(ethylene glycol).
2001-09-11
[Involuntary movement disorders as first manifestation of systemic lupus erythematosus: case report].
2001-09
[Efficacy of anticonvulsants on acute encephalitis with refractory, repetitive partial seizures (AERRPS)].
2001-09
Topiramate as a mood stabilizer.
2001-09
Hyperekplexia in neonates.
2001-09
Spectrofluorimetric determination of vigabatrin and gabapentin in dosage forms and spiked plasma samples through derivatization with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole.
2001-08-15
Gamma irradiation effects on stability of poly(lactide-co-glycolide) microspheres containing clonazepam.
2001-08-10
[Primary orthostatic tremor: slow harmonic component as responsible of inestability].
2001-08-04
Burning mouth syndrome after taking clonazepam.
2001-08-04
Role of clonazepam in the treatment of idiopathic downbeat nystagmus.
2001-08
Benzodiazepines protect against ethanol-induced gastric mucosal damage in vitro.
2001-08
Carbamazepine treatment of corticosteroid-induced mood disorder.
2001-08
Nonconvulsive status epilepticus associated with cephalosporins in patients with renal failure.
2001-08
Smoking and panic disorder.
2001-08
A 28-year-old woman with panic disorder.
2001-07-25
Case report: unexplained syncope explained.
2001-07
Infantile status epilepticus in Tunisia. Clinical, etiological and prognostic aspects.
2001-07
Involuntary movements in infantile cobalamin deficiency appearing after treatment.
2001-07
Sleep disorders.
2001-02
Pharmacological options for the treatment of Tourette's disorder.
2001
Burning mouth syndrome.
2001
Psychiatric disorders associated with Cushing's syndrome. Epidemiology, pathophysiology and treatment.
2001
LSD-induced Hallucinogen Persisting Perception Disorder treated with clonazepam: two case reports.
2001
Sleep disorders in patients with Parkinson's disease: epidemiology and management.
2001
Patents

Patents

04014916
10
JP2007525670A
150
JPH04202186A
2

Sample Use Guides

In Vivo Use Guide
Seizure Disorders: Adults: The initial dose for adults with seizure disorders should not exceed 1.5 mg/day divided into three doses. Dosage may be increased in increments of 0.5 to 1 mg every 3 days until seizures are adequately controlled or until side effects preclude any further increase. Maintenance dosage must be individualized for each patient depending upon response. Maximum recommended daily dose is 20 mg. Clonazepam is available as a tablet or an orally disintegrating tablet (wafer). The tablets should be administered with water by swallowing the tablet whole. The orally disintegrating tablet should be administered as follows: After opening the pouch, peel back the foil on the blister. Do not push tablet through foil. Immediately upon opening the blister, using dry hands, remove the tablet and place it in the mouth. Tablet disintegration occurs rapidly in saliva so it can be easily swallowed with or without water.
Route of Administration: Oral
In Vitro Use Guide
Clonazepam (100 nM) increased inhibitory postsynaptic current (IPSC) decay time constants in rat thalamic nuclei-the reticular nucleus (nRt) (from 44.3 to 77.9 ms, P < 0.01) but not in the ventrobasal (VB) complex..
Substance Class Chemical
Created
by admin
on Wed Apr 02 11:07:40 GMT 2025
Edited
by admin
on Wed Apr 02 11:07:40 GMT 2025
Record UNII
XXQ3A82WUX
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CLONAZEPAM HYDROCHLORIDE
Common Name English
2H-1,4-BENZODIAZEPIN-2-ONE, 5-(2-CHLOROPHENYL)-1,3-DIHYDRO-7-NITRO-, HYDROCHLORIDE (1:1)
Preferred Name English
2H-1,4-BENZODIAZEPIN-2-ONE, 5-(2-CHLOROPHENYL)-1,3-DIHYDRO-7-NITRO-, MONOHYDROCHLORIDE
Systematic Name English
Code System Code Type Description
SMS_ID
300000038751
Created by admin on Wed Apr 02 11:07:40 GMT 2025 , Edited by admin on Wed Apr 02 11:07:40 GMT 2025
PRIMARY
CAS
61321-60-6
Created by admin on Wed Apr 02 11:07:40 GMT 2025 , Edited by admin on Wed Apr 02 11:07:40 GMT 2025
PRIMARY
PUBCHEM
67937833
Created by admin on Wed Apr 02 11:07:40 GMT 2025 , Edited by admin on Wed Apr 02 11:07:40 GMT 2025
PRIMARY
FDA UNII
XXQ3A82WUX
Created by admin on Wed Apr 02 11:07:40 GMT 2025 , Edited by admin on Wed Apr 02 11:07:40 GMT 2025
PRIMARY
Related Record Type Details
Structure of Clonazepam
PARENT -> SALT/SOLVATE
Related Record Type Details
Structure of Clonazepam
ACTIVE MOIETY
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