Details
Stereochemistry | ACHIRAL |
Molecular Formula | C18H19ClN4 |
Molecular Weight | 326.8239 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CN1CCN(CC1)C2=Nc3cc(ccc3Nc4ccccc42)Cl
InChI
InChIKey=QZUDBNBUXVUHMW-UHFFFAOYSA-N
InChI=1S/C18H19ClN4/c1-22-8-10-23(11-9-22)18-14-4-2-3-5-15(14)20-16-7-6-13(19)12-17(16)21-18/h2-7,12,20H,8-11H2,1H3
DescriptionCurator's Comment:: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/10372606
Curator's Comment:: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/10372606
Clozapine was discovered in 1958 by an anesthetist and now it is used for the treatment of schizophrenia. Although the exact mechanism of its action is unknown, the effect of clozapine on schizophrenia is associated with inhibition of dopamine D2 and serotonin 2A receptors.
CNS Activity
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL217 |
160.0 nM [Ki] | ||
Target ID: CHEMBL224 |
5.4 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | CLOZARIL Approved UseClozaril is an atypical antipsychotic indicated for: Treatment-resistant schizophrenia. Launch Date6.2277118E11 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
98 nM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/10606838 |
12.5 mg single, oral dose: 12.5 mg route of administration: Oral experiment type: SINGLE co-administered: |
CLOZAPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
319 ng/mL |
100 mg 2 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CLOZAPINE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1348 nM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/10606838 |
12.5 mg single, oral dose: 12.5 mg route of administration: Oral experiment type: SINGLE co-administered: |
CLOZAPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
18.6 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/10606838 |
12.5 mg single, oral dose: 12.5 mg route of administration: Oral experiment type: SINGLE co-administered: |
CLOZAPINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
12 h |
100 mg 2 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CLOZAPINE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3% |
100 mg 2 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CLOZAPINE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
289 mg 1 times / day multiple, oral (mean) Recommended Dose: 289 mg, 1 times / day Route: oral Route: multiple Dose: 289 mg, 1 times / day Sources: |
unhealthy, 41 n = 22 Health Status: unhealthy Condition: refractory psychotic mania Age Group: 41 Sex: M+F Population Size: 22 Sources: |
Other AEs: Sedation, Salivation... Other AEs: Sedation (14 patients) Sources: Salivation (6 patients) Constipation (6 patients) Nausea and vomiting (5 patients) Dizziness (4 patients) Fever (4 patients) |
296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Disc. AE: Orthostatic hypotension, Sedation... Other AEs: Sedation, Hypersalivation... AEs leading to discontinuation/dose reduction: Orthostatic hypotension (13 patients) Other AEs:Sedation (1 patient) Dysphagia (1 patient) Fever (2 patients) Tachycardia (2 patients) Myocarditis (1 patient) Leukopenia (3 patients) Parkinsonism (1 patient) Myocardial infarction (3 patients) Ataxia (1 patient) Cardiomyopathy (1 patient) Sedation (28 patients) Sources: Hypersalivation (25 patients) Constipation (16 patients) Weight gain (8 patients) Leukopenia (4 patients) Tachycardia (3 patients) Leukopenia (2 patients) Seizure (2 patients) Dysphagia (1 patient) Fever (1 patient) Fatigue (1 patient) |
450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Other AEs: Dry mouth, Urinary hesitancy... Other AEs: Dry mouth (20%) Sources: Urinary hesitancy (10%) Constipation (60%) Nausea (60%) Dyspepsia (70%) Headache (40%) Somnolence (100%) Lethargy (90%) Myoclonus (30%) Stuttering (20%) Sialorrhea (80%) Sweating (50%) Urinary frequency (40%) Dysphagia (20%) Orthostatic hypotension (10%) Dizziness (60%) Increased appetite (50%) |
900 mg 1 times / day multiple, oral (max) Recommended Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: |
unhealthy, adult n = 126 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 126 Sources: |
Other AEs: Drowsiness, Tachycardia... Other AEs: Drowsiness (21%) Sources: Tachycardia (17%) Constipation (16%) Dizziness (14%) Hypotension (13%) Hyperthermia (13%) Salivation (13%) Hypertension (12%) Headache (10%) Nausea and vomiting (10%) Dry mouth (5%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Sedation | 14 patients | 289 mg 1 times / day multiple, oral (mean) Recommended Dose: 289 mg, 1 times / day Route: oral Route: multiple Dose: 289 mg, 1 times / day Sources: |
unhealthy, 41 n = 22 Health Status: unhealthy Condition: refractory psychotic mania Age Group: 41 Sex: M+F Population Size: 22 Sources: |
Dizziness | 4 patients | 289 mg 1 times / day multiple, oral (mean) Recommended Dose: 289 mg, 1 times / day Route: oral Route: multiple Dose: 289 mg, 1 times / day Sources: |
unhealthy, 41 n = 22 Health Status: unhealthy Condition: refractory psychotic mania Age Group: 41 Sex: M+F Population Size: 22 Sources: |
Fever | 4 patients | 289 mg 1 times / day multiple, oral (mean) Recommended Dose: 289 mg, 1 times / day Route: oral Route: multiple Dose: 289 mg, 1 times / day Sources: |
unhealthy, 41 n = 22 Health Status: unhealthy Condition: refractory psychotic mania Age Group: 41 Sex: M+F Population Size: 22 Sources: |
Nausea and vomiting | 5 patients | 289 mg 1 times / day multiple, oral (mean) Recommended Dose: 289 mg, 1 times / day Route: oral Route: multiple Dose: 289 mg, 1 times / day Sources: |
unhealthy, 41 n = 22 Health Status: unhealthy Condition: refractory psychotic mania Age Group: 41 Sex: M+F Population Size: 22 Sources: |
Constipation | 6 patients | 289 mg 1 times / day multiple, oral (mean) Recommended Dose: 289 mg, 1 times / day Route: oral Route: multiple Dose: 289 mg, 1 times / day Sources: |
unhealthy, 41 n = 22 Health Status: unhealthy Condition: refractory psychotic mania Age Group: 41 Sex: M+F Population Size: 22 Sources: |
Salivation | 6 patients | 289 mg 1 times / day multiple, oral (mean) Recommended Dose: 289 mg, 1 times / day Route: oral Route: multiple Dose: 289 mg, 1 times / day Sources: |
unhealthy, 41 n = 22 Health Status: unhealthy Condition: refractory psychotic mania Age Group: 41 Sex: M+F Population Size: 22 Sources: |
Dysphagia | 1 patient | 296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Fatigue | 1 patient | 296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Fever | 1 patient | 296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Ataxia | 1 patient Disc. AE |
296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Cardiomyopathy | 1 patient Disc. AE |
296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Dysphagia | 1 patient Disc. AE |
296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Myocarditis | 1 patient Disc. AE |
296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Parkinsonism | 1 patient Disc. AE |
296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Sedation | 1 patient Disc. AE |
296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Orthostatic hypotension | 13 patients Disc. AE |
296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Constipation | 16 patients | 296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Leukopenia | 2 patients | 296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Seizure | 2 patients | 296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Fever | 2 patients Disc. AE |
296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Tachycardia | 2 patients Disc. AE |
296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Hypersalivation | 25 patients | 296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Sedation | 28 patients | 296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Tachycardia | 3 patients | 296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Leukopenia | 3 patients Disc. AE |
296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Myocardial infarction | 3 patients Disc. AE |
296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Leukopenia | 4 patients | 296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Weight gain | 8 patients | 296 mg 1 times / day multiple, oral (mean) Recommended Dose: 296 mg, 1 times / day Route: oral Route: multiple Dose: 296 mg, 1 times / day Sources: |
unhealthy, 74.2 years (range: 65-89 years) n = 75 Health Status: unhealthy Condition: schizophrenia | schizoaffective disorder | Parkinson’ s disease with psychotic symptoms | bipolar disorder | acquired brain injury Age Group: 74.2 years (range: 65-89 years) Sex: M+F Population Size: 75 Sources: |
Orthostatic hypotension | 10% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Urinary hesitancy | 10% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Somnolence | 100% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Dry mouth | 20% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Dysphagia | 20% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Stuttering | 20% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Myoclonus | 30% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Headache | 40% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Urinary frequency | 40% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Increased appetite | 50% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Sweating | 50% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Constipation | 60% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Dizziness | 60% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Nausea | 60% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Dyspepsia | 70% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Sialorrhea | 80% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Lethargy | 90% | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: |
unhealthy, adult n = 10 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 10 Sources: |
Headache | 10% | 900 mg 1 times / day multiple, oral (max) Recommended Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: |
unhealthy, adult n = 126 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 126 Sources: |
Nausea and vomiting | 10% | 900 mg 1 times / day multiple, oral (max) Recommended Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: |
unhealthy, adult n = 126 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 126 Sources: |
Hypertension | 12% | 900 mg 1 times / day multiple, oral (max) Recommended Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: |
unhealthy, adult n = 126 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 126 Sources: |
Hyperthermia | 13% | 900 mg 1 times / day multiple, oral (max) Recommended Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: |
unhealthy, adult n = 126 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 126 Sources: |
Hypotension | 13% | 900 mg 1 times / day multiple, oral (max) Recommended Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: |
unhealthy, adult n = 126 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 126 Sources: |
Salivation | 13% | 900 mg 1 times / day multiple, oral (max) Recommended Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: |
unhealthy, adult n = 126 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 126 Sources: |
Dizziness | 14% | 900 mg 1 times / day multiple, oral (max) Recommended Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: |
unhealthy, adult n = 126 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 126 Sources: |
Constipation | 16% | 900 mg 1 times / day multiple, oral (max) Recommended Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: |
unhealthy, adult n = 126 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 126 Sources: |
Tachycardia | 17% | 900 mg 1 times / day multiple, oral (max) Recommended Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: |
unhealthy, adult n = 126 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 126 Sources: |
Drowsiness | 21% | 900 mg 1 times / day multiple, oral (max) Recommended Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: |
unhealthy, adult n = 126 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 126 Sources: |
Dry mouth | 5% | 900 mg 1 times / day multiple, oral (max) Recommended Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: |
unhealthy, adult n = 126 Health Status: unhealthy Condition: schizophrenia, treatment-resistant Age Group: adult Sex: M+F Population Size: 126 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
yes [IC50 42 uM] | ||||
yes [Ki 19 uM] | ||||
yes [Ki 31 uM] | ||||
yes [Ki 69 uM] | ||||
yes [Ki 99 uM] | ||||
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
major | yes (co-administration study) Comment: co-administration with fluvoxamin lead to 3x increase in clozapine Cmin |
|||
minor | ||||
minor | ||||
minor | ||||
minor | weak (co-administration study) Comment: co-administration studies indicate modest (<2x) increase in clozapine exposure when co-administered with CYP3A4 inhibitors |
|||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | yes (pharmacogenomic study) Comment: UGT1A1*28 and UGT1A4*3 alleles contribute significantly to inter-individual variability in CLZ and dmCLZ metabolism Sources: https://pubmed.ncbi.nlm.nih.gov/22565219/ |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
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PubMed
Title | Date | PubMed |
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Hepatic encephalopathy associated with combined clozapine and divalproex sodium treatment. | 1997 Apr |
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A selective dopamine D4 receptor antagonist, NRA0160: a preclinical neuropharmacological profile. | 1999 |
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Clozapine lacks previous clinical efficacy when restarted after a period of discontinuation: a case series. | 1999 Dec |
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Clozapine pretreatment modifies haloperidol-elicited forebrain Fos induction: a regionally-specific double dissociation. | 1999 Jun |
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New and old antipsychotics versus clozapine in a monkey model: adverse effects and antiamphetamine effects. | 1999 Jun |
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Seizures after discontinuation of low-dose lorazepam from originally seizure-free clozapine regimen: combined effects? | 1999 Jun |
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Clozapine and obsessions in patients with recent-onset schizophrenia and other psychotic disorders. | 1999 Jun |
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[Presentation of obsessive-compulsive symptoms in a patient with schizophrenia treated with clozapine]. | 1999 May |
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Quinpirole, 8-OH-DPAT and ketanserin modulate catalepsy induced by high doses of atypical antipsychotics. | 1999 Nov |
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Worsening of motor features of parkinsonism with olanzapine. | 1999 Nov |
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[The concept of supersensitivity psychosis. The particular case of clozapine]. | 1999 Nov-Dec |
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Clozapine, neuroleptic malignant syndrome, and pancerebellar syndrome. | 1999 Nov-Dec |
|
Hypotension associated with clozapine after cardiopulmonary bypass. | 1999 Oct |
|
Clozapine-induced acute interstitial nephritis. | 1999 Oct 2 |
|
Transient syncope and ECG changes associated with the concurrent administration of clozapine and diazepam. | 1999 Sep |
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Reemergence of tardive dyskinesia after discontinuation of clozapine treatment. | 2000 Dec 15 |
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An unexpected and serious complication of treatment with the atypical antipsychotic drug clozapine. | 2000 Jul |
|
Clozapine-associated extrapyramidal reaction. | 2000 May |
|
Significant interaction between clozapine and cocaine in cocaine addicts. | 2000 May 1 |
|
Ciprofloxacin increases serum clozapine and N-desmethylclozapine: a study in patients with schizophrenia. | 2000 Nov |
|
A case of pharmacokinetic interference in comedication of clozapine and valproic acid. | 2000 Nov |
|
Hyperglycemia, hyperlipemia, and periodic paralysis: a case report of new side effects of clozapine. | 2000 Nov |
|
Risperidone-associated hyperprolactinemia. | 2000 Nov-Dec |
|
Inverse agonist activity of atypical antipsychotic drugs at human 5-hydroxytryptamine2C receptors. | 2000 Oct |
|
Effects of antipsychotic drugs on cholecystokinin and preprotachykinin (substance P) mRNA expression in the rat hippocampal formation. | 2000 Sep |
|
Myotoxicity and neurotoxicity during clozapine treatment. | 2000 Sep-Oct |
|
Antipsychotic medications and the elderly: effects on cognition and implications for use. | 2001 |
|
Combinations of clozapine and phencyclidine: effects on drug discrimination and behavioral inhibition in rats. | 2001 |
|
Protein thiol oxidation by haloperidol results in inhibition of mitochondrial complex I in brain regions: comparison with atypical antipsychotics. | 2001 Apr |
|
New onset diabetes and atypical antipsychotics. | 2001 Feb |
|
Effects of newer atypical antipsychotics on autonomic neurocardiac function: a comparison between amisulpride, olanzapine, sertindole, and clozapine. | 2001 Feb |
|
Uncompetitive antagonists of the N-methyl-D-aspartate (NMDA) receptors alter the mRNA expression of proteins associated with the NMDA receptor complex. | 2001 Feb |
|
Clozapine-associated reduction in arrest rates of psychotic patients with criminal histories. | 2001 Feb |
|
Haloperidol and clozapine increase neural activity in the rat prefrontal cortex. | 2001 Feb 9 |
|
Olanzapine-induced leukopenia with human leukocyte antigen profiling. | 2001 Jan |
|
Pharmacokinetic-pharmacodynamic modelling in the early development phase of anti-psychotics: a comparison of the effects of clozapine, S 16924 and S 18327 in the EEG model in rats. | 2001 Jan |
|
Genetic determinants of clozapine-induced agranulocytosis: recent results of HLA subtyping in a non-jewish caucasian sample. | 2001 Jan |
|
Trimethoprim-sulfamethoxazole and clozapine. | 2001 Jan |
|
Clozapine therapy for a patient with a history of Hodgkin's disease. | 2001 Jan |
|
The clozapine access project. | 2001 Jan |
|
Pharmacology of [3H]R(+)-7-OH-DPAT binding in the rat caudate-putamen. | 2001 Jan |
|
Double-blind comparison of olanzapine versus clozapine in schizophrenic patients clinically eligible for treatment with clozapine. | 2001 Jan 1 |
|
Antipsychotic drugs classified by their effects on the release of dopamine and noradrenaline in the prefrontal cortex and striatum. | 2001 Jan 26 |
|
A proposed pathological model in the hippocampus of subjects with schizophrenia. | 2001 Jan-Feb |
|
Electroconvulsive therapy in rehabilitation: the Hong Kong experience. | 2001 Mar |
|
Clozapine and pulmonary embolus. | 2001 Mar |
|
Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics?: A new hypothesis. | 2001 Mar |
|
Pharmacological characterization of locomotor sensitization induced by chronic phencyclidine administration. | 2001 Mar |
|
Double activity imaging reveals distinct cellular targets of haloperidol, clozapine and dopamine D(3) receptor selective RGH-1756. | 2001 Mar |
|
The dynamin-dependent, arrestin-independent internalization of 5-hydroxytryptamine 2A (5-HT2A) serotonin receptors reveals differential sorting of arrestins and 5-HT2A receptors during endocytosis. | 2001 Mar 16 |
Sample Use Guides
Start with 12.5 mg once daily or twice daily, then increase the total daily dosage in increments of 25 mg to 50 mg per day (if well-tolerated) in order to reach 300 mg to 450 mg per day, in divided doses, by the end of 2 weeks.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25477781
The effects of antipsychotic medication on the energy metabolism of OLN-93 cells were analyzed by adding a vehicle (0.01% HCl, same dissolving solution used to solubilize the antipsychotics), 1 or 10 ug/ml of clozapine to the cell culture for 6 or 24 h.
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Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
357411
Created by
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NCI_THESAURUS |
C29710
Created by
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LIVERTOX |
230
Created by
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NDF-RT |
N0000175430
Created by
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NCI_THESAURUS |
C94726
Created by
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WHO-VATC |
QN05AH02
Created by
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WHO-ATC |
N05AH02
Created by
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Code System | Code | Type | Description | ||
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722
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PRIMARY | |||
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38
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PRIMARY | |||
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5786-21-0
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PRIMARY | |||
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CLOZARIL
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PRIMARY | APPROVED APRIL 2009 | ||
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D003024
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PRIMARY | |||
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M3676
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PRIMARY | Merck Index | ||
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DB00363
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PRIMARY | |||
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6478
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PRIMARY | |||
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1333667-72-3
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ALTERNATIVE | |||
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1142107
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PRIMARY | USP-RS | ||
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CLOZAPINE
Created by
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PRIMARY | |||
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135398737
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PRIMARY | |||
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Clozapine
Created by
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5786-21-0
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PRIMARY | |||
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2612
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PRIMARY | |||
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J60AR2IKIC
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PRIMARY | |||
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SUB06787MIG
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PRIMARY | |||
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2626
Created by
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PRIMARY | RxNorm | ||
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227-313-7
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PRIMARY | |||
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CHEMBL42
Created by
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PRIMARY | |||
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C28936
Created by
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PRIMARY | |||
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1142108
Created by
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PRIMARY | USP-RS |
ACTIVE MOIETY
METABOLITE ACTIVE (PARENT)
METABOLITE LESS ACTIVE (PARENT)
SALT/SOLVATE (PARENT)