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Details

Stereochemistry ACHIRAL
Molecular Formula C18H18ClNOS
Molecular Weight 331.86
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ZOTEPINE

SMILES

CN(C)CCOC1=CC2=C(SC3=CC=C(Cl)C=C13)C=CC=C2

InChI

InChIKey=HDOZVRUNCMBHFH-UHFFFAOYSA-N
InChI=1S/C18H18ClNOS/c1-20(2)9-10-21-16-11-13-5-3-4-6-17(13)22-18-8-7-14(19)12-15(16)18/h3-8,11-12H,9-10H2,1-2H3

HIDE SMILES / InChI
Molecular Formula C18H18ClNOS
Molecular Weight 331.86
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Zotepine is a potent antipsychotic and antidepressive drug, which was developed in Japan and used in many countries for the treatment of schizophrenia. Zotepine has high affinity to D2, 5-HT2A, 5-HT2C, 5-HT6, 5-HT7, alpha1A, H1, and D1 receptors at therapeutically relevant concentrations and has similar affinities to 5-HT1A, alpha2A, and M1 receptors at high concentrations. In human zotepine is metabolized to a major metabolite, norzotepine, which has profile similar to that of zotepine for important neurotransmitter receptors known to be responsible for zotepine antipsychotic activity.The drug is still available in Asia.

CNS Activity

Originator

Approval Year

Unknown
149124
Targets

Targets

Primary TargetPharmacologyConditionPotency
5-hydroxytryptamine receptor 2A
73
Target ID: P28223
Gene ID: 3356.0
Gene Symbol: HTR2A
Target Organism: Homo sapiens (Human)
Antagonist
2849
 0.69 nM [Ki]
5-hydroxytryptamine receptor 2C
29
Target ID: P28335
Gene ID: 3358.0
Gene Symbol: HTR2C
Target Organism: Homo sapiens (Human)
Antagonist
2849
 1.29 nM [Ki]
D(2) dopamine receptor
58
Target ID: P14416
Gene ID: 1813.0
Gene Symbol: DRD2
Target Organism: Homo sapiens (Human)
Antagonist
2849
 2.3 nM [Ki]
5-hydroxytryptamine receptor 6
10
Target ID: P50406
Gene ID: 3362.0
Gene Symbol: HTR6
Target Organism: Homo sapiens (Human)
Antagonist
2849
 2.9 nM [Ki]
Alpha-1A adrenergic receptor
22
Target ID: P35348|||B0ZBD9|||Q6RUJ8
Gene ID: 148.0
Gene Symbol: ADRA1A
Target Organism: Homo sapiens (Human)
Antagonist
2849
 1.2 nM [Ki]
5-hydroxytryptamine receptor 7
16
Target ID: P34969
Gene ID: 3363.0
Gene Symbol: HTR7
Target Organism: Homo sapiens (Human)
Antagonist
2849
 4.6 nM [Ki]
Histamine H1 receptor
316
Target ID: P35367
Gene ID: 3269.0
Gene Symbol: HRH1
Target Organism: Homo sapiens (Human)
Antagonist
2849
 0.47 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8583
LODOPIN

Approved Use

Schizophrenia.
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
7.8 ng/mL
OTHER GOV'T
https://www.info.pmda.go.jp/go/interview/4/171911_1179024C1033_4_002_1F.pdf#page=22 | https://www.sciencedirect.com/science/article/pii/S0924977X98806068
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ZOTEPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
13.2 ng/mL
OTHER GOV'T
https://www.info.pmda.go.jp/go/interview/4/171911_1179024C1033_4_002_1F.pdf#page=22 | https://www.sciencedirect.com/science/article/pii/S0924977X98806068
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ZOTEPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
30.9 ng/mL
OTHER GOV'T
https://www.info.pmda.go.jp/go/interview/4/171911_1179024C1033_4_002_1F.pdf#page=22 | https://www.sciencedirect.com/science/article/pii/S0924977X98806068
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ZOTEPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
123 ng × h/mL
OTHER GOV'T
https://www.info.pmda.go.jp/go/interview/4/171911_1179024C1033_4_002_1F.pdf#page=22 | https://www.sciencedirect.com/science/article/pii/S0924977X98806068
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ZOTEPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
159 ng × h/mL
OTHER GOV'T
https://www.info.pmda.go.jp/go/interview/4/171911_1179024C1033_4_002_1F.pdf#page=22 | https://www.sciencedirect.com/science/article/pii/S0924977X98806068
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ZOTEPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
316.3 ng × h/mL
OTHER GOV'T
https://www.info.pmda.go.jp/go/interview/4/171911_1179024C1033_4_002_1F.pdf#page=22 | https://www.sciencedirect.com/science/article/pii/S0924977X98806068
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ZOTEPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
14.1 h
OTHER GOV'T
https://www.info.pmda.go.jp/go/interview/4/171911_1179024C1033_4_002_1F.pdf#page=22 | https://www.sciencedirect.com/science/article/pii/S0924977X98806068
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ZOTEPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
12.8 h
OTHER GOV'T
https://www.info.pmda.go.jp/go/interview/4/171911_1179024C1033_4_002_1F.pdf#page=22 | https://www.sciencedirect.com/science/article/pii/S0924977X98806068
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ZOTEPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
13 h
OTHER GOV'T
https://www.info.pmda.go.jp/go/interview/4/171911_1179024C1033_4_002_1F.pdf#page=22 | https://www.sciencedirect.com/science/article/pii/S0924977X98806068
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ZOTEPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
3%
OTHER GOV'T
https://www.info.pmda.go.jp/go/interview/4/171911_1179024C1033_4_002_1F.pdf#page=25
ZOTEPINE serum
Homo sapiens
3%
REVIEW
https://pubmed.ncbi.nlm.nih.gov/20486863/
ZOTEPINE plasma
Homo sapiens
Doses

Doses

DosePopulationAdverse events​
397.1 mg 1 times / day multiple, oral
Highest studied dose
Dose: 397.1 mg, 1 times / day
Route: oral
Route: multiple
Dose: 397.1 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/23422395/
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/23422395/
Disc. AE: Seizure, Psychotic behavior...
AEs leading to
discontinuation/dose reduction:
Seizure (2.9%)
Psychotic behavior (17.1%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/23422395/
131 mg 1 times / day multiple, oral
Recommended
Dose: 131 mg, 1 times / day
Route: oral
Route: multiple
Dose: 131 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/15551193/
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/15551193/
Disc. AE: Psychosis, Retching...
AEs leading to
discontinuation/dose reduction:
Psychosis (grade 3, 2.6%)
Retching (2.6%)
Nausea (2.6%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/15551193/
AEs

AEs

AESignificanceDosePopulation
Psychotic behavior 17.1%
Disc. AE
397.1 mg 1 times / day multiple, oral
Highest studied dose
Dose: 397.1 mg, 1 times / day
Route: oral
Route: multiple
Dose: 397.1 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/23422395/
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/23422395/
Seizure 2.9%
Disc. AE
397.1 mg 1 times / day multiple, oral
Highest studied dose
Dose: 397.1 mg, 1 times / day
Route: oral
Route: multiple
Dose: 397.1 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/23422395/
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/23422395/
Nausea 2.6%
Disc. AE
131 mg 1 times / day multiple, oral
Recommended
Dose: 131 mg, 1 times / day
Route: oral
Route: multiple
Dose: 131 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/15551193/
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/15551193/
Retching 2.6%
Disc. AE
131 mg 1 times / day multiple, oral
Recommended
Dose: 131 mg, 1 times / day
Route: oral
Route: multiple
Dose: 131 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/15551193/
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/15551193/
Psychosis grade 3, 2.6%
Disc. AE
131 mg 1 times / day multiple, oral
Recommended
Dose: 131 mg, 1 times / day
Route: oral
Route: multiple
Dose: 131 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/15551193/
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/15551193/
PubMed

PubMed

TitleDatePubMed
Prolonged withdrawal delirium in concomitant diphenhydramine and nefopam dependence: A case report.
2010-05-30
QTc prolongation and antipsychotic medications in a sample of 1017 patients with schizophrenia.
2010-03-17
Gene expression of NMDA receptor subunits in the cerebellum of elderly patients with schizophrenia.
2010-03
Zotepine versus other atypical antipsychotics for schizophrenia.
2010-01-20
Quetiapine versus other atypical antipsychotics for schizophrenia.
2010-01-20
Amisulpride versus other atypical antipsychotics for schizophrenia.
2010-01-20
First-generation vs second-generation antipsychotic drugs: The ongoing saga.
2010-01
Increased D-amino acid oxidase expression in the bilateral hippocampal CA4 of schizophrenic patients: a post-mortem study.
2009-12
Ziprasidone versus other atypical antipsychotics for schizophrenia.
2009-10-07
Aripiprazole versus other atypical antipsychotics for schizophrenia.
2009-10-07
Application of on-line electrochemistry/electrospray/tandem mass spectrometry to a quantification method for the antipsychotic drug zotepine in human serum.
2009-10
Impaired prefrontal hemodynamic maturation in autism and unaffected siblings.
2009-09-03
Effects of zotepine on extracellular levels of monoamine, GABA and glutamate in rat prefrontal cortex.
2009-06
Sertindole versus other atypical antipsychotics for schizophrenia.
2009-04-15
Further characterization of the discriminative stimulus properties of the atypical antipsychotic drug clozapine in C57BL/6 mice: role of 5-HT(2A) serotonergic and alpha (1) adrenergic antagonism.
2009-04
Review of the efficacy of placebo in comparative clinical trials between typical and atypical antipsychotics.
2009-03
Zotepine: a clinical review.
2009-02
A meta-analysis of head-to-head comparisons of second-generation antipsychotics in the treatment of schizophrenia.
2009-02
The effect of antipsychotic medication on sexual function and serum prolactin levels in community-treated schizophrenic patients: results from the Schizophrenia Trial of Aripiprazole (STAR) study (NCT00237913).
2008-12-22
Zotepine-induced spontaneous ejaculation.
2008-11
Zotepine-induced QTc prolongation.
2008-10
A pharmacoeconomic analysis of atypical antipsychotics and haloperidol in first-episode schizophrenic patients in taiwan.
2008-06
[Atypical antipsychotics in first-episode psychosis: a review].
2008-04
Treatment of clozapine-associated tardive dyskinesia.
2008-02-15
Cardiac side effects of psychiatric drugs.
2008-01
Acute and long-term treatment of mania.
2008
Typical and atypical antipsychotics--the misleading dichotomy. Results from the Working Group 'Drugs in Psychiatry' (AGATE).
2008
Current therapeutic options for Alzheimer's disease.
2007-12
Differences in the effect of second-generation antipsychotics on prolactinaemia: six weeks open-label trial in female in-patients.
2007-12
Pharmacological causes of hyperprolactinemia.
2007-10
Early prediction of clinical response in schizophrenia patients receiving the atypical antipsychotic zotepine.
2007-10
Are there any differences in the efficacy among second generation antipsychotics in the treatment of schizophrenia and related disorders?
2007-07-07
Atypical antipsychotic drugs: current issues of safety and efficacy in the management of schizophrenia.
2007-07
Hypothermia following antipsychotic drug use.
2007-06
Simultaneous prescribing of atypical antipsychotics, conventional antipsychotics and anticholinergics-a European study.
2007-06
Second-generation antipsychotic agents in the treatment of acute mania: a systematic review and meta-analysis of randomized controlled trials.
2007-04
Risk of extrapyramidal syndrome in schizophrenic patients treated with antipsychotics: a population-based study.
2007-04
Long-acting risperidone injection: efficacy, safety, and cost-effectiveness of the first long-acting atypical antipsychotic.
2007-02
Atypical antipsychotics to treat the neuropsychiatric symptoms of dementia.
2006-12
Quantitative determination of forty-eight antidepressants and antipsychotics in human serum by HPLC tandem mass spectrometry: a multi-level, single-sample approach.
2006-10-20
Zotepine for schizophrenia.
2006-10-18
Efficacy and safety of zotepine for patients with treatment-resistant schizophrenia.
2006-10
[Trazodone for the treatment of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease: a retrospective study focused on the aggression and negativism in caregiving situations].
2006-06
Investigation of the electrochemical oxidation products of zotepine and their fragmentation using on-line electrochemistry/electrospray ionization mass spectrometry.
2006-05
Perazine for schizophrenia.
2006-04-19
The effectiveness of atypical antipsychotics for the treatment of aggression and psychosis in Alzheimer's disease.
2006-01-25
Adverse effects of atypical antipsychotics in the elderly: a review.
2006
Effect of zotepine on dopamine, serotonin and noradrenaline release in rat prefrontal cortex.
2005-12-28
Schizophrenia.
2005-12
[The serotonin syndrome].
2005-10
Patents

Patents

US4443469 A
1

Sample Use Guides

In Vivo Use Guide
The usual adult dosage for oral use is 75 mg to 150 mg of zotepine daily in divided doses.
Route of Administration: Oral
In Vitro Use Guide
Unknown
Substance Class Chemical
Created
by admin
on Mon Mar 31 18:05:00 GMT 2025
Edited
by admin
on Mon Mar 31 18:05:00 GMT 2025
Record UNII
U29O83JAZW
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ZOTEPINE
INN   JAN   MART.   MI   WHO-DD  
INN  
Official Name English
NIPOLEPT
Preferred Name English
Zotepine [WHO-DD]
Common Name English
ZOTEPIN
Common Name English
ZOTEPINE [MART.]
Common Name English
2-((8-CHLORODIBENZO(B,F)THIEPIN-10-YL)OXY)-N,N-DIMETHYLETHYLAMINE
Systematic Name English
ZOTEPINE [MI]
Common Name English
SETOUS
Brand Name English
zotepine [INN]
Common Name English
ZOTEPINE [JAN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C66885
Created by admin on Mon Mar 31 18:05:00 GMT 2025 , Edited by admin on Mon Mar 31 18:05:00 GMT 2025
WHO-VATC QN05AX11
Created by admin on Mon Mar 31 18:05:00 GMT 2025 , Edited by admin on Mon Mar 31 18:05:00 GMT 2025
WHO-ATC N05AX11
Created by admin on Mon Mar 31 18:05:00 GMT 2025 , Edited by admin on Mon Mar 31 18:05:00 GMT 2025
NCI_THESAURUS C66883
Created by admin on Mon Mar 31 18:05:00 GMT 2025 , Edited by admin on Mon Mar 31 18:05:00 GMT 2025
Code System Code Type Description
INN
4112
Created by admin on Mon Mar 31 18:05:00 GMT 2025 , Edited by admin on Mon Mar 31 18:05:00 GMT 2025
PRIMARY
NCI_THESAURUS
C81096
Created by admin on Mon Mar 31 18:05:00 GMT 2025 , Edited by admin on Mon Mar 31 18:05:00 GMT 2025
PRIMARY
EVMPD
SUB00191MIG
Created by admin on Mon Mar 31 18:05:00 GMT 2025 , Edited by admin on Mon Mar 31 18:05:00 GMT 2025
PRIMARY
ChEMBL
CHEMBL285802
Created by admin on Mon Mar 31 18:05:00 GMT 2025 , Edited by admin on Mon Mar 31 18:05:00 GMT 2025
PRIMARY
CAS
26615-21-4
Created by admin on Mon Mar 31 18:05:00 GMT 2025 , Edited by admin on Mon Mar 31 18:05:00 GMT 2025
PRIMARY
MESH
C022172
Created by admin on Mon Mar 31 18:05:00 GMT 2025 , Edited by admin on Mon Mar 31 18:05:00 GMT 2025
PRIMARY
DRUG BANK
DB09225
Created by admin on Mon Mar 31 18:05:00 GMT 2025 , Edited by admin on Mon Mar 31 18:05:00 GMT 2025
PRIMARY
SMS_ID
100000091930
Created by admin on Mon Mar 31 18:05:00 GMT 2025 , Edited by admin on Mon Mar 31 18:05:00 GMT 2025
PRIMARY
WIKIPEDIA
ZOTEPINE
Created by admin on Mon Mar 31 18:05:00 GMT 2025 , Edited by admin on Mon Mar 31 18:05:00 GMT 2025
PRIMARY
CHEBI
32316
Created by admin on Mon Mar 31 18:05:00 GMT 2025 , Edited by admin on Mon Mar 31 18:05:00 GMT 2025
PRIMARY
FDA UNII
U29O83JAZW
Created by admin on Mon Mar 31 18:05:00 GMT 2025 , Edited by admin on Mon Mar 31 18:05:00 GMT 2025
PRIMARY
MERCK INDEX
m11667
Created by admin on Mon Mar 31 18:05:00 GMT 2025 , Edited by admin on Mon Mar 31 18:05:00 GMT 2025
PRIMARY Merck Index
EPA CompTox
DTXSID9023756
Created by admin on Mon Mar 31 18:05:00 GMT 2025 , Edited by admin on Mon Mar 31 18:05:00 GMT 2025
PRIMARY
PUBCHEM
5736
Created by admin on Mon Mar 31 18:05:00 GMT 2025 , Edited by admin on Mon Mar 31 18:05:00 GMT 2025
PRIMARY
RXCUI
40003
Created by admin on Mon Mar 31 18:05:00 GMT 2025 , Edited by admin on Mon Mar 31 18:05:00 GMT 2025
PRIMARY RxNorm
IUPHAR
103
Created by admin on Mon Mar 31 18:05:00 GMT 2025 , Edited by admin on Mon Mar 31 18:05:00 GMT 2025
PRIMARY
DRUG CENTRAL
2875
Created by admin on Mon Mar 31 18:05:00 GMT 2025 , Edited by admin on Mon Mar 31 18:05:00 GMT 2025
PRIMARY
Related Record Type Details
ALPHA-2A ADRENERGIC RECEPTOR
TARGET -> AGONIST
Related Record Type Details
Structure of ZOTEPINE
ACTIVE MOIETY
NIH
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