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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
Structure of CLOZAPINE

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

HIDE SMILES / InChI

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

Description
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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
CLOZARIL

Approved Use

Clozaril is an atypical antipsychotic indicated for: Treatment-resistant schizophrenia.

Launch Date

6.2277118E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
98 nM
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

AUC

ValueDoseCo-administeredAnalytePopulation
1348 nM × h
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

T1/2

ValueDoseCo-administeredAnalytePopulation
18.6 h
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

Funbound

ValueDoseCo-administeredAnalytePopulation
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

Doses

DosePopulationAdverse 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)
Salivation (6 patients)
Constipation (6 patients)
Nausea and vomiting (5 patients)
Dizziness (4 patients)
Fever (4 patients)
Sources:
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)
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)
Other AEs:
Sedation (28 patients)
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)
Sources:
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%)
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%)
Sources:
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%)
Tachycardia (17%)
Constipation (16%)
Dizziness (14%)
Hypotension (13%)
Hyperthermia (13%)
Salivation (13%)
Hypertension (12%)
Headache (10%)
Nausea and vomiting (10%)
Dry mouth (5%)
Sources:
AEs

AEs

AESignificanceDosePopulation
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:
OverviewDrug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
yes (co-administration study)
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
Tox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
A selective dopamine D4 receptor antagonist, NRA0160: a preclinical neuropharmacological profile.
1999
Comparison of dopamine receptor antagonists on hyperlocomotion induced by cocaine, amphetamine, MK-801 and the dopamine D1 agonist C-APB in mice.
1999 Aug
The emergence of social phobia during clozapine treatment and its response to fluoxetine augmentation.
1999 Dec
Clozapine lacks previous clinical efficacy when restarted after a period of discontinuation: a case series.
1999 Dec
New and old antipsychotics versus clozapine in a monkey model: adverse effects and antiamphetamine effects.
1999 Jun
Clozapine and obsessions in patients with recent-onset schizophrenia and other psychotic disorders.
1999 Jun
[Neuroleptic malignant syndrome after treatment with olanzapine].
1999 Mar 8
The cytotoxicity of clozapine metabolites: implications for predicting clozapine-induced agranulocytosis.
1999 May
Quinpirole, 8-OH-DPAT and ketanserin modulate catalepsy induced by high doses of atypical antipsychotics.
1999 Nov
Worsening of motor features of parkinsonism with olanzapine.
1999 Nov
Myocarditis and cardiomyopathy associated with clozapine.
1999 Nov 27
[The concept of supersensitivity psychosis. The particular case of clozapine].
1999 Nov-Dec
Could discontinuing smoking be hazardous for patients administered clozapine medication? A case report.
1999 Oct
Clozapine-induced acute interstitial nephritis.
1999 Oct 2
Possible tardive dystonia resulting from clozapine therapy.
1999 Sep
Citalopram and clozapine: potential drug interaction.
2000 Apr
Anticholinergic differences among patients receiving standard clinical doses of olanzapine or clozapine.
2000 Jun
Gabapentin prophylaxis of clozapine-induced seizures.
2000 Mar
Clozapine-associated extrapyramidal reaction.
2000 May
Significant interaction between clozapine and cocaine in cocaine addicts.
2000 May 1
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
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
A naturalistic comparison of clozapine, risperidone, and olanzapine in the treatment of bipolar disorder.
2000 Sep
Effects of antipsychotic drugs on cholecystokinin and preprotachykinin (substance P) mRNA expression in the rat hippocampal formation.
2000 Sep
Quetiapine for l-dopa-induced psychosis in PD.
2000 Sep 26
Myotoxicity and neurotoxicity during clozapine treatment.
2000 Sep-Oct
Antipsychotic medications and the elderly: effects on cognition and implications for use.
2001
Olanzapine: an updated review of its use in the management of schizophrenia.
2001
Atypical antipsychotics: new directions and new challenges in the treatment of schizophrenia.
2001
Combinations of clozapine and phencyclidine: effects on drug discrimination and behavioral inhibition in rats.
2001
Possible serotonin syndrome associated with clomipramine after withdrawal of clozapine.
2001 Feb
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
FosB in rat striatum: normal regional distribution and enhanced expression after 6-month haloperidol administration.
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
Olanzapine-induced leukopenia with human leukocyte antigen profiling.
2001 Jan
The clozapine access project.
2001 Jan
Fatty acid derivatives of clozapine: prolonged antidopaminergic activity of docosahexaenoylclozapine in the rat.
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
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
Cloning, expression, and pharmacological characterization of a novel human histamine receptor.
2001 Mar
Patents

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
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 Fri Dec 15 15:07:36 UTC 2023
Edited
by admin
on Fri Dec 15 15:07:36 UTC 2023
Record UNII
J60AR2IKIC
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CLOZAPINE
EP   HSDB   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP   VANDF   WHO-DD  
USAN   INN  
Official Name English
CLOZAPINE [JAN]
Common Name English
LEPONEX
Brand Name English
8-Chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo[b,e][1,4]diazepine
Systematic Name English
CLOZAPINE [USP-RS]
Common Name English
CLOZAPINE [MI]
Common Name English
CLOZAPINE (CLOZARIL) [VANDF]
Common Name English
CLOZAPINE (FAZACLO) [VANDF]
Common Name English
CLOZAPINE [USAN]
Common Name English
CLOZAPINE RESOLUTION MIXTURE [USP-RS]
Common Name English
CLOZARIL
Brand Name English
CLOZAPINE [USP MONOGRAPH]
Common Name English
CLOZAPINE [HSDB]
Common Name English
HF-1854
Code English
FAZACLO
Brand Name English
clozapine [INN]
Common Name English
CLOZAPINE (VERSACLOZ) [VANDF]
Common Name English
CLOZAPINE [EP MONOGRAPH]
Common Name English
Clozapine [WHO-DD]
Common Name English
CLOZAPINE RESOLUTION MIXTURE
USP-RS  
Common Name English
CLOZAPINE (IVAX) [VANDF]
Common Name English
5H-DIBENZO(B,E)(1,4)DIAZEPINE, 8-CHLORO-11-(4-METHYL-1-PIPERAZINYL)-
Systematic Name English
NSC-757429
Code English
CLOZAPINE (CARACO) [VANDF]
Common Name English
HF 1854
Code English
CLOZAPINE (MYLAN) [VANDF]
Common Name English
CLOZAPINE [VANDF]
Common Name English
CLOZAPINE (UDL) [VANDF]
Common Name English
CLOZAPINE (TEVA) [VANDF]
Common Name English
CLOZAPINE [MART.]
Common Name English
CLOZAPINE [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 357411
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
NCI_THESAURUS C29710
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
LIVERTOX NBK548412
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
NDF-RT N0000175430
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
NCI_THESAURUS C94726
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
WHO-VATC QN05AH02
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
WHO-ATC N05AH02
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
Code System Code Type Description
DRUG CENTRAL
722
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
PRIMARY
IUPHAR
38
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
PRIMARY
EPA CompTox
DTXSID5022855
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
PRIMARY
JAPANESE REVIEW
CLOZARIL
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
PRIMARY APPROVED APRIL 2009
MESH
D003024
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
PRIMARY
MERCK INDEX
m3676
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
PRIMARY Merck Index
DRUG BANK
DB00363
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
PRIMARY
HSDB
6478
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
PRIMARY
CAS
1333667-72-3
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
ALTERNATIVE
CHEBI
3766
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
PRIMARY
SMS_ID
100000092795
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
PRIMARY
WIKIPEDIA
CLOZAPINE
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
PRIMARY
PUBCHEM
135398737
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
PRIMARY
LACTMED
Clozapine
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
PRIMARY
RS_ITEM_NUM
1142107
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
PRIMARY
NSC
757429
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
PRIMARY
CAS
5786-21-0
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
PRIMARY
INN
2612
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
PRIMARY
FDA UNII
J60AR2IKIC
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
PRIMARY
EVMPD
SUB06787MIG
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
PRIMARY
RXCUI
2626
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
PRIMARY RxNorm
ECHA (EC/EINECS)
227-313-7
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
PRIMARY
ChEMBL
CHEMBL42
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
PRIMARY
NCI_THESAURUS
C28936
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 UTC 2023
PRIMARY
DAILYMED
J60AR2IKIC
Created by admin on Fri Dec 15 15:07:36 UTC 2023 , Edited by admin on Fri Dec 15 15:07:36 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