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Details

Stereochemistry ACHIRAL
Molecular Formula C15H10ClN3O3
Molecular Weight 315.7117
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CLONAZEPAM

SMILES

c1ccc(c(c1)C2=NCC(=Nc3ccc(cc32)N(=O)=O)O)Cl

InChI

InChIKey=DGBIGWXXNGSACT-UHFFFAOYSA-N
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)

HIDE SMILES / InChI
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

1.71071996E11
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

1.71071996E11
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
Obstructive sleep apnea syndrome induced by clonazepam in a narcoleptic patient with REM-sleep-behavior disorder.
1999 Dec
Efficacy, safety, and gradual discontinuation of clonazepam in panic disorder: a placebo-controlled, multicenter study using optimized dosages.
1999 Sep
Cognitive functions after pilocarpine-induced status epilepticus: changes during silent period precede appearance of spontaneous recurrent seizures.
1999 Sep
Influence of LY 300164, an antagonist of AMPA/kainate receptors, on the anticonvulsant activity of clonazepam.
1999 Sep 10
Seizure-inducing paradoxical reaction to antiepileptic drugs.
2000 Jun
Pharmacological options for the treatment of Tourette's disorder.
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
Benzodiazepines and anticonvulsants for social phobia (social anxiety disorder).
2001
Asymptomatic QTc prolongation associated with quetiapine fumarate overdose in a patient being treated with risperidone.
2001 Apr
Random total antiepileptic drug levels and seizure control during pregnancy.
2001 Apr
Expression of the peripheral-type benzodiazepine receptor and apoptosis induction in hepatic stellate cells.
2001 Apr
Role of clonazepam in the treatment of idiopathic downbeat nystagmus.
2001 Aug
Benzodiazepines protect against ethanol-induced gastric mucosal damage in vitro.
2001 Aug
Carbamazepine treatment of corticosteroid-induced mood disorder.
2001 Aug
Gamma irradiation effects on stability of poly(lactide-co-glycolide) microspheres containing clonazepam.
2001 Aug 10
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
Pharmacological characterization of the 6 Hz psychomotor seizure model of partial epilepsy.
2001 Dec
Roles for mitochondrial and reverse mode Na+/Ca2+ exchange and the plasmalemma Ca2+ ATPase in post-tetanic potentiation at crayfish neuromuscular junctions.
2001 Dec 15
Focal stiff-person syndrome.
2001 Feb
Acute effect of different antidepressants on glycemia in diabetic and non-diabetic rats.
2001 Jan
Case report: unexplained syncope explained.
2001 Jul
Infantile status epilepticus in Tunisia. Clinical, etiological and prognostic aspects.
2001 Jul
Early coadministration of clonazepam with sertraline for panic disorder.
2001 Jul
Diazepam stimulates migration and phagocytosis of human neutrophils: possible contribution of peripheral-type benzodiazepine receptors and intracellular calcium.
2001 Jul
Melatonin therapy for REM sleep behavior disorder.
2001 Jun
Obstetrical and neonatal outcome following clonazepam use during pregnancy: a case series.
2001 May-Jun
Stiff leg syndrome: case report.
2001 Nov
West syndrome: the Philippine experience.
2001 Nov
Increased [Mg2+]o reduces Ca2+ influx and disruption of mitochondrial membrane potential during reoxygenation.
2001 Nov
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
Evaluation of in vitro percutaneous absorption of lorazepam and clonazepam from hydro-alcoholic gel formulations.
2001 Oct 9
[Involuntary movement disorders as first manifestation of systemic lupus erythematosus: case report].
2001 Sep
[Efficacy of anticonvulsants on acute encephalitis with refractory, repetitive partial seizures (AERRPS)].
2001 Sep
Topiramate as a mood stabilizer.
2001 Sep
[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
Spectrofluorimetric determination of vigabatrin and gabapentin in urine and dosage forms through derivatization with fluorescamine.
2002 Jan 1
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..
Name Type Language
CLONAZEPAM
EP   HSDB   INN   MART.   MI   ORANGE BOOK   USAN   USP   VANDF   WHO-DD  
USAN   INN  
Official Name English
NSC-179913
Code English
CLONAZEPAM [JAN]
Common Name English
RIVOTRIL
Brand Name English
RO-5-4023
Code English
CLONAZEPAM [MART.]
Common Name English
RIVATRIL
Brand Name English
RO 5-4023
Code English
2H-1,4-BENZODIAZEPIN-2-ONE, 5-(2-CHLOROPHENYL)-1,3-DIHYDRO-7-NITRO-
Systematic Name English
CLONAZEPAM [ORANGE BOOK]
Common Name English
5-(O-CHLOROPHENYL)-1,3-DIHYDRO-7-NITRO-2H-1,4-BENZODIAZEPIN-2-ONE
Common Name English
CLONAZEPAM [MI]
Common Name English
KLONOPIN
Brand Name English
CLONAZEPAM [EP MONOGRAPH]
Common Name English
RO-54023
Code English
CLONAZEPAM [WHO-DD]
Common Name English
CLONAZEPAM [INN]
Common Name English
RAVOTRIL
Brand Name English
CLONAZEPAM [VANDF]
Common Name English
CLONAZEPAM CIV [USP-RS]
Common Name English
CLONAZEPAM [HSDB]
Common Name English
CLONAZEPAM CIV
USP-RS  
Common Name English
CLONAZEPAM [USAN]
Common Name English
CLONAZEPAM [USP MONOGRAPH]
Common Name English
Classification Tree Code System Code
NDF-RT N0000175694
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
WHO-VATC QN03AE01
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
NCI_THESAURUS C264
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
FDA ORPHAN DRUG 243507
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
WHO-ATC N03AE01
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
NDF-RT N0000007542
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
NCI_THESAURUS C1012
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
DEA NO. 2737
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
LIVERTOX 224
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
FDA ORPHAN DRUG 82794
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
Code System Code Type Description
PUBCHEM
2802
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
PRIMARY
WIKIPEDIA
CLONAZEPAM
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
PRIMARY
RXCUI
2598
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
PRIMARY RxNorm
DRUG CENTRAL
703
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
PRIMARY
LACTMED
Clonazepam
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
PRIMARY
DRUG BANK
DB01068
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
PRIMARY
CAS
1622-61-3
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
PRIMARY
MESH
D002998
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
PRIMARY
MERCK INDEX
M3649
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
PRIMARY Merck Index
USP_CATALOG
1140305
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
PRIMARY USP-RS
ECHA (EC/EINECS)
216-596-2
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
PRIMARY
EPA CompTox
1622-61-3
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
PRIMARY
INN
2765
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
PRIMARY
NCI_THESAURUS
C28935
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
PRIMARY
FDA UNII
5PE9FDE8GB
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
PRIMARY
EVMPD
SUB06728MIG
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
PRIMARY
ChEMBL
CHEMBL452
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
PRIMARY
HSDB
3265
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
PRIMARY
IUPHAR
6963
Created by admin on Fri Jun 25 20:53:24 UTC 2021 , Edited by admin on Fri Jun 25 20:53:24 UTC 2021
PRIMARY