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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=CC2=C(NC(=O)CN=C2C3=C(Cl)C=CC=C3)C=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 ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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
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
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
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
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
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
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%
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:
healthy, 30 years (range: 23–50 years)
n = 12
Health Status: healthy
Age Group: 30 years (range: 23–50 years)
Sex: M+F
Population Size: 12
Sources:
2 mg single, intravenous
Dose: 2 mg
Route: intravenous
Route: single
Dose: 2 mg
Sources:
healthy, 30 years (range: 23–50 years)
n = 12
Health Status: healthy
Age Group: 30 years (range: 23–50 years)
Sex: M+F
Population Size: 12
Sources:
2 mg single, oral
Dose: 2 mg
Route: oral
Route: single
Dose: 2 mg
Sources:
healthy, 30 years (range: 23–50 years)
n = 12
Health Status: healthy
Age Group: 30 years (range: 23–50 years)
Sex: M+F
Population Size: 12
Sources:
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:
unhealthy
n = 574
Health Status: unhealthy
Condition: seizure disorders
Population Size: 574
Sources:
Disc. AE: Somnolence, Depression...
AEs leading to
discontinuation/dose reduction:
Somnolence (7%)
Depression (4%)
Nervousness (1%)
Dizziness (1%)
Ataxia (1%)
Intellectual disability (1%)
Sources:
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:
unhealthy
Health Status: unhealthy
Condition: depression
Sources:
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:
unhealthy
n = 574
Health Status: unhealthy
Condition: seizure disorders
Population Size: 574
Sources:
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:
unhealthy
n = 574
Health Status: unhealthy
Condition: seizure disorders
Population Size: 574
Sources:
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:
unhealthy
n = 574
Health Status: unhealthy
Condition: seizure disorders
Population Size: 574
Sources:
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:
unhealthy
n = 574
Health Status: unhealthy
Condition: seizure disorders
Population Size: 574
Sources:
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:
unhealthy
n = 574
Health Status: unhealthy
Condition: seizure disorders
Population Size: 574
Sources:
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:
unhealthy
n = 574
Health Status: unhealthy
Condition: seizure disorders
Population Size: 574
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer







Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
yes
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.
PubMed

PubMed

TitleDatePubMed
Pharmacological options for the treatment of Tourette's disorder.
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
Insomnia and fronto-basal tumor: a case report.
2001
[Clonazepam in the treatment of labile arterial hypertension in the elderly].
2001
Treatment of typical absence seizures and related epileptic syndromes.
2001
Tourette syndrome: clinical characteristics and current management strategies.
2001
Hyposecretion of the adrenal androgen dehydroepiandrosterone sulfate and its relation to clinical variables in inflammatory arthritis.
2001
Sensitivity to the effects of sedative-hypnotics on motor performance: influence of task difficulty and chronic phenobarbital administration.
2001 Apr
Semiautomated high-performance liquid chromatographic method for the determination of benzodiazepines in whole blood.
2001 Apr
Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD): acute placebo-controlled sleep laboratory studies with clonazepam.
2001 Apr
Expression of the peripheral-type benzodiazepine receptor and apoptosis induction in hepatic stellate cells.
2001 Apr
Benzodiazepines protect against ethanol-induced gastric mucosal damage in vitro.
2001 Aug
Nonconvulsive status epilepticus associated with cephalosporins in patients with renal failure.
2001 Aug
Smoking and panic disorder.
2001 Aug
Mitochondria recycle Ca(2+) to the endoplasmic reticulum and prevent the depletion of neighboring endoplasmic reticulum regions.
2001 Aug 3
[Primary orthostatic tremor: slow harmonic component as responsible of inestability].
2001 Aug-Sep
Pharmacoepidemiologic investigation of a clonazepam-carbamazepine interaction by mixed effect modeling using routine clinical pharmacokinetic data in Japanese patients.
2001 Dec
Direct LC analysis of five benzodiazepines in human urine and plasma using an ADS restricted access extraction column.
2001 Dec
Focal stiff-person syndrome.
2001 Feb
[Cortico-subcortical electrophysiological study during the effects of benzodiazepines in patients with panic disorders].
2001 Feb 16-28
Case report: unexplained syncope explained.
2001 Jul
Infantile status epilepticus in Tunisia. Clinical, etiological and prognostic aspects.
2001 Jul
Involuntary movements in infantile cobalamin deficiency appearing after treatment.
2001 Jul
Early coadministration of clonazepam with sertraline for panic disorder.
2001 Jul
Burning mouth syndrome after taking clonazepam.
2001 Jul-Aug
Melatonin therapy for REM sleep behavior disorder.
2001 Jun
Interaction of GYKI 52466, a selective non-competitive antagonist of AMPA/kainate receptors, with conventional antiepileptic drugs in amygdala-kindled seizures in rats.
2001 Mar-Apr
Behavioral effects of agents active at the gamma-aminobutyric acid receptor complex in the staircase paradigm.
2001 May 18
Obstetrical and neonatal outcome following clonazepam use during pregnancy: a case series.
2001 May-Jun
Stiff leg syndrome: case report.
2001 Nov
Fast orthostatic tremor in Parkinson's disease mimicking primary orthostatic tremor.
2001 Nov
Kinetic and pharmacological properties of GABA(A) receptors in single thalamic neurons and GABA(A) subunit expression.
2001 Nov
Successful use of methadone in the treatment of chronic neuropathic pain arising from burn injuries: a case-study.
2001 Nov
Determination of benzodiazepines in human hair by on-line high-performance liquid chromatography using a restricted access extraction column.
2001 Nov 15
Population pharmacokinetic analysis resulting in a tool for dose individualization of busulphan in bone marrow transplantation recipients.
2001 Oct
Influence of age and comedication on steady-state clonazepam serum level-dose ratios in Japanese epileptic patients.
2001 Oct
Diazepam inhibits HIV-1 Tat-induced migration of human microglia.
2001 Oct
2-Arylpyrazolo[1,5-a]pyrimidin-3-yl acetamides. New potent and selective peripheral benzodiazepine receptor ligands.
2001 Oct
Effect of clonazepam treatment on antipsychotic drug-induced Meige syndrome and changes in plasma levels of GABA, HVA, and MHPG during treatment.
2001 Oct
A successful clonazepam treatment without tolerance in a patient with spontaneous oral dyskinesia.
2001 Oct
[Involuntary movement disorders as first manifestation of systemic lupus erythematosus: case report].
2001 Sep
Hyperekplexia in neonates.
2001 Sep
Evaluation of polymeric nanoparticles composed of cholic acid and methoxy poly(ethylene glycol).
2001 Sep 11
Effect of midazolam on interleukin-6 mRNA expression in human peripheral blood mononuclear cells in the absence of lipopolysaccharide.
2001 Sep 21
[Treatment and long-term follow-up of post-anoxic myoclonus].
2001 Sep 23
Burning mouth syndrome.
2001 Summer
Myoclonus during prolonged treatment with sertraline in an adolescent patient.
2001 Summer
Effects of commonly used benzodiazepines on the fetus, the neonate, and the nursing infant.
2002 Jan
Patents

Sample Use Guides

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
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 Sat Dec 16 18:25:24 GMT 2023
Edited
by admin
on Sat Dec 16 18:25:24 GMT 2023
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-, MONOHYDROCHLORIDE
Systematic Name English
2H-1,4-BENZODIAZEPIN-2-ONE, 5-(2-CHLOROPHENYL)-1,3-DIHYDRO-7-NITRO-, HYDROCHLORIDE (1:1)
Systematic Name English
Code System Code Type Description
SMS_ID
300000038751
Created by admin on Sat Dec 16 18:25:24 GMT 2023 , Edited by admin on Sat Dec 16 18:25:24 GMT 2023
PRIMARY
CAS
61321-60-6
Created by admin on Sat Dec 16 18:25:24 GMT 2023 , Edited by admin on Sat Dec 16 18:25:24 GMT 2023
PRIMARY
PUBCHEM
67937833
Created by admin on Sat Dec 16 18:25:24 GMT 2023 , Edited by admin on Sat Dec 16 18:25:24 GMT 2023
PRIMARY
FDA UNII
XXQ3A82WUX
Created by admin on Sat Dec 16 18:25:24 GMT 2023 , Edited by admin on Sat Dec 16 18:25:24 GMT 2023
PRIMARY
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