Details
Stereochemistry | ACHIRAL |
Molecular Formula | C18H19ClN4 |
Molecular Weight | 326.823 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CN1CCN(CC1)C2=NC3=C(NC4=C2C=CC=C4)C=CC(Cl)=C3
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
Molecular Formula | C18H19ClN4 |
Molecular Weight | 326.823 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
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 |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
The emergence of social phobia during clozapine treatment and its response to fluoxetine augmentation. | 1999 Dec |
|
New and old antipsychotics versus clozapine in a monkey model: adverse effects and antiamphetamine effects. | 1999 Jun |
|
D1 receptor blockade improves L-dopa-induced dyskinesia but worsens parkinsonism in MPTP monkeys. | 1999 Mar 10 |
|
Clozapine, neuroleptic malignant syndrome, and pancerebellar syndrome. | 1999 Nov-Dec |
|
Reemergence of tardive dyskinesia after discontinuation of clozapine treatment. | 2000 Dec 15 |
|
Hyperglycemia, hyperlipemia, and periodic paralysis: a case report of new side effects of clozapine. | 2000 Nov |
|
Inverse agonist activity of atypical antipsychotic drugs at human 5-hydroxytryptamine2C receptors. | 2000 Oct |
|
Contrasting patterns and cellular specificity of transcriptional regulation of the nuclear receptor nerve growth factor-inducible B by haloperidol and clozapine in the rat forebrain. | 2000 Oct |
|
Olanzapine: an updated review of its use in the management of schizophrenia. | 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 |
|
Is generic really the same? | 2001 Feb |
|
Bodyweight gain with atypical antipsychotics. A comparative review. | 2001 Jan |
|
Clozapine, but not haloperidol, reverses social behavior deficit in mice during withdrawal from chronic phencyclidine treatment. | 2001 Jan 22 |
|
Electroconvulsive therapy in rehabilitation: the Hong Kong experience. | 2001 Mar |
|
Atypical antipsychotics and hyperglycaemia. | 2001 Mar |
|
Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics?: A new hypothesis. | 2001 Mar |
|
Cloning, expression, and pharmacological characterization of a novel human histamine receptor. | 2001 Mar |
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.
Substance Class |
Chemical
Created
by
admin
on
Edited
Wed Jul 05 22:39:29 UTC 2023
by
admin
on
Wed Jul 05 22:39:29 UTC 2023
|
Record UNII |
J60AR2IKIC
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Common Name | English | ||
|
Brand Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Brand Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Brand Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English |
Classification Tree | Code System | Code | ||
---|---|---|---|---|
|
FDA ORPHAN DRUG |
357411
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
||
|
NCI_THESAURUS |
C29710
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
||
|
LIVERTOX |
NBK548412
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
||
|
NDF-RT |
N0000175430
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
||
|
NCI_THESAURUS |
C94726
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
||
|
WHO-VATC |
QN05AH02
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
||
|
WHO-ATC |
N05AH02
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
722
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
PRIMARY | |||
|
38
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
PRIMARY | |||
|
DTXSID5022855
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
PRIMARY | |||
|
CLOZARIL
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
PRIMARY | APPROVED APRIL 2009 | ||
|
D003024
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
PRIMARY | |||
|
M3676
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
PRIMARY | Merck Index | ||
|
DB00363
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
PRIMARY | |||
|
6478
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
PRIMARY | |||
|
1333667-72-3
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
ALTERNATIVE | |||
|
3766
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
PRIMARY | |||
|
100000092795
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
PRIMARY | |||
|
CLOZAPINE
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
PRIMARY | |||
|
135398737
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
PRIMARY | |||
|
Clozapine
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
PRIMARY | |||
|
1142107
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
PRIMARY | |||
|
757429
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
PRIMARY | |||
|
5786-21-0
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
PRIMARY | |||
|
2612
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
PRIMARY | |||
|
J60AR2IKIC
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
PRIMARY | |||
|
SUB06787MIG
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
PRIMARY | |||
|
2626
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
PRIMARY | RxNorm | ||
|
227-313-7
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
PRIMARY | |||
|
CHEMBL42
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
PRIMARY | |||
|
C28936
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
PRIMARY | |||
|
J60AR2IKIC
Created by
admin on Wed Jul 05 22:39:29 UTC 2023 , Edited by admin on Wed Jul 05 22:39:29 UTC 2023
|
PRIMARY |
Related Record | Type | Details | ||
---|---|---|---|---|
|
METABOLIC ENZYME -> INHIBITOR |
IC50
|
||
|
BINDER->LIGAND |
BINDING
|
||
|
TARGET -> INHIBITOR |
IC50
|
||
|
METABOLIC ENZYME -> SUBSTRATE | |||
|
SALT/SOLVATE -> PARENT |
|
||
|
TARGET -> INHIBITOR |
Ki
|
Related Record | Type | Details | ||
---|---|---|---|---|
|
METABOLITE ACTIVE -> PARENT |
ACTIVITY OF NORCLOZAPINE AGAINST DOPAMINE AND SEROTONIN RECEPTOR MAY DIFFER FROM THAT OF CLOZAPINE
MAJOR
|
||
|
METABOLITE LESS ACTIVE -> PARENT |
MAJOR
|
||
|
METABOLITE LESS ACTIVE -> PARENT |
APPEARS TO HAVE LESS ACTIVITY THAN CLOZAPINE AND NORCLOZAPINE AGAINST 5HT RECEPTORS
MAJOR
|
||
|
METABOLITE ACTIVE -> PARENT |
MAJOR
Significant Metabolite
|
Related Record | Type | Details | ||
---|---|---|---|---|
|
IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
CLINICALLY SIGNIFICANT
|
||
|
IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
|
||
|
IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
|
||
|
IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
|
Related Record | Type | Details | ||
---|---|---|---|---|
|
ACTIVE MOIETY |
|
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
---|---|---|---|---|---|---|
Biological Half-life | PHARMACOKINETIC |
|
|
|||