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
Molecular Formula | C18H19ClN4 |
Molecular Weight | 326.8239 |
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 |
---|---|---|
Panic disorder associated with clozapine. | 2000 Dec |
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Reemergence of tardive dyskinesia after discontinuation of clozapine treatment. | 2000 Dec 15 |
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Ciprofloxacin increases serum clozapine and N-desmethylclozapine: a study in patients with schizophrenia. | 2000 Nov |
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A case of pharmacokinetic interference in comedication of clozapine and valproic acid. | 2000 Nov |
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Hyperglycemia, hyperlipemia, and periodic paralysis: a case report of new side effects of clozapine. | 2000 Nov |
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Risperidone-associated hyperprolactinemia. | 2000 Nov-Dec |
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Myotoxicity and neurotoxicity during clozapine treatment. | 2000 Sep-Oct |
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Antipsychotic medications and the elderly: effects on cognition and implications for use. | 2001 |
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Olanzapine: an updated review of its use in the management of schizophrenia. | 2001 |
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Effects of systemic injections of dopaminergic agents on the habituation of rats submitted to an open field test. | 2001 |
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Evidence for an association between polymorphism in the serotonin-2A receptor variant (102T/C) and increment of N100 amplitude in schizophrenics treated with clozapine. | 2001 |
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Atypical antipsychotics: new directions and new challenges in the treatment of schizophrenia. | 2001 |
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Combinations of clozapine and phencyclidine: effects on drug discrimination and behavioral inhibition in rats. | 2001 |
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Protein thiol oxidation by haloperidol results in inhibition of mitochondrial complex I in brain regions: comparison with atypical antipsychotics. | 2001 Apr |
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New onset diabetes and atypical antipsychotics. | 2001 Feb |
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Is generic really the same? | 2001 Feb |
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Possible serotonin syndrome associated with clomipramine after withdrawal of clozapine. | 2001 Feb |
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Effects of newer atypical antipsychotics on autonomic neurocardiac function: a comparison between amisulpride, olanzapine, sertindole, and clozapine. | 2001 Feb |
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Mitchell B. Balter Award. Human leukocyte antigen-A1 predicts a good therapeutic response to clozapine with a low risk of agranulocytosis in patients with schizophrenia. | 2001 Feb |
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FosB in rat striatum: normal regional distribution and enhanced expression after 6-month haloperidol administration. | 2001 Feb |
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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 increases apolipoprotein D expression in rodent brain: towards a mechanism for neuroleptic pharmacotherapy. | 2001 Feb |
|
Subspecialty training in schizophrenia. | 2001 Feb |
|
Increased dopamine d(2) receptor occupancy and elevated prolactin level associated with addition of haloperidol to clozapine. | 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 |
|
Bodyweight gain with atypical antipsychotics. A comparative review. | 2001 Jan |
|
Clozapine for the treatment of drug-induced psychosis in Parkinson's disease: results of the 12 week open label extension in the PSYCLOPS trial. | 2001 Jan |
|
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 |
|
Fatty acid derivatives of clozapine: prolonged antidopaminergic activity of docosahexaenoylclozapine in the rat. | 2001 Jan |
|
The effect of clozapine on caudate nucleus volume in schizophrenic patients previously treated with typical antipsychotics. | 2001 Jan |
|
Double-blind comparison of olanzapine versus clozapine in schizophrenic patients clinically eligible for treatment with clozapine. | 2001 Jan 1 |
|
Lack of association between the T-->C 267 serotonin 5-HT6 receptor gene (HTR6) polymorphism and prediction of response to clozapine in schizophrenia. | 2001 Jan 15 |
|
Clozapine, but not haloperidol, reverses social behavior deficit in mice during withdrawal from chronic phencyclidine treatment. | 2001 Jan 22 |
|
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 |
|
5-HT(2A) and D(2) receptor blockade increases cortical DA release via 5-HT(1A) receptor activation: a possible mechanism of atypical antipsychotic-induced cortical dopamine release. | 2001 Mar |
|
Atypical antipsychotics and hyperglycaemia. | 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 |
|
Cloning, expression, and pharmacological characterization of a novel human histamine receptor. | 2001 Mar |
|
Cloning and pharmacological characterization of a fourth histamine receptor (H(4)) expressed in bone marrow. | 2001 Mar |
|
Double activity imaging reveals distinct cellular targets of haloperidol, clozapine and dopamine D(3) receptor selective RGH-1756. | 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
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on
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Fri Jun 25 21:00:20 UTC 2021
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Record UNII |
J60AR2IKIC
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Record Status |
Validated (UNII)
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Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
357411
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NCI_THESAURUS |
C29710
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LIVERTOX |
230
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NDF-RT |
N0000175430
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NCI_THESAURUS |
C94726
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WHO-VATC |
QN05AH02
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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
Created by
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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
Created by
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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
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PRIMARY | |||
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5786-21-0
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2612
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J60AR2IKIC
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SUB06787MIG
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PRIMARY | |||
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2626
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PRIMARY | RxNorm | ||
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227-313-7
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PRIMARY | |||
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CHEMBL42
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PRIMARY | |||
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C28936
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PRIMARY | |||
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1142108
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PRIMARY | USP-RS |
Related Record | Type | Details | ||
---|---|---|---|---|
|
METABOLIC ENZYME -> INHIBITOR |
IC50
|
||
|
BINDER->LIGAND |
BINDING
|
||
|
TARGET -> INHIBITOR | |||
|
METABOLIC ENZYME -> SUBSTRATE | |||
|
SALT/SOLVATE -> PARENT | |||
|
TARGET -> INHIBITOR |
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 | ||
---|---|---|---|---|
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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