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
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
| 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.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
| 0.06 nM [EC50] | |||
Target ID: CHEMBL2095172 |
57.0 µM [EC50] | ||
Target ID: CHEMBL2111413 |
40.0 µM [EC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | KLONOPIN Approved UseINDICATIONS & 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 Date1975 |
|||
| Primary | KLONOPIN Approved UseINDICATIONS & 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 Date1975 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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
| Dose | Population | Adverse 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 |
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%) Sources: Depression (4%) Nervousness (1%) Dizziness (1%) Ataxia (1%) Intellectual disability (1%) |
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 |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| 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
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no | ||||
| no | ||||
| no | ||||
| weak | ||||
| yes |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical 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
| Title | Date | PubMed |
|---|---|---|
| Serum clonazepam concentrations in children with absence seizures. | 1975 Mar |
|
| Benztropine for venlafaxine-induced night sweats. | 2000 Apr |
|
| Effects of anticonvulsants on local anaesthetic-induced neurotoxicity in rats. | 2000 Feb |
|
| Cerebellar Ataxia. | 2000 May |
|
| Pharmacological options for the treatment of Tourette's disorder. | 2001 |
|
| LSD-induced Hallucinogen Persisting Perception Disorder treated with clonazepam: two case reports. | 2001 |
|
| Insomnia and fronto-basal tumor: a case report. | 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 |
|
| [Clonazepam in therapy of neurogenic syncopal states]. | 2001 |
|
| Sensitivity to the effects of sedative-hypnotics on motor performance: influence of task difficulty and chronic phenobarbital administration. | 2001 Apr |
|
| Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD): acute placebo-controlled sleep laboratory studies with clonazepam. | 2001 Apr |
|
| Nonconvulsive status epilepticus associated with cephalosporins in patients with renal failure. | 2001 Aug |
|
| Pharmacoepidemiologic investigation of a clonazepam-carbamazepine interaction by mixed effect modeling using routine clinical pharmacokinetic data in Japanese patients. | 2001 Dec |
|
| Pharmacological characterization of the 6 Hz psychomotor seizure model of partial epilepsy. | 2001 Dec |
|
| Focal stiff-person syndrome. | 2001 Feb |
|
| Treatment of bipolar depression with twice-weekly fluoxetine: management of antidepressant-induced mania. | 2001 Jan |
|
| Acute effect of different antidepressants on glycemia in diabetic and non-diabetic rats. | 2001 Jan |
|
| Involuntary movements in infantile cobalamin deficiency appearing after treatment. | 2001 Jul |
|
| Acquired epileptiform opercular syndrome: a case report and results of single photon emission computed tomography and computer-assisted electroencephalographic analysis. | 2001 Jul |
|
| Peripheral-type benzodiazepine receptor ligands: mitochondrial permeability transition induction in rat cardiac tissue. | 2001 Mar 15 |
|
| 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 |
|
| Successful use of methadone in the treatment of chronic neuropathic pain arising from burn injuries: a case-study. | 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 |
|
| 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 |
|
| Topiramate as a mood stabilizer. | 2001 Sep |
|
| 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 |
|
| 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
| Substance Class |
Chemical
Created
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| Record UNII |
XXQ3A82WUX
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| Record Status |
Validated (UNII)
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| Record Version |
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61321-60-6
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67937833
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PARENT -> SALT/SOLVATE |
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ACTIVE MOIETY |
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