Identification

Name
Zotepine
Accession Number
DB09225
Type
Small Molecule
Groups
Approved, Investigational, Withdrawn
Description

Zotepine, with the formula (2-chloro-11-(2-dimethyl-amino-ethoxy)-dibenzo thiepin, is a neuroleptic drug. It was designed and synthesized by Fujisawa Pharmaceutical Co Ltd.[1] It has been used as an antipsychotic in Japan, India and some places in Europe like UK and Germany since 1980's.[2] Zotepine was never approved by the FDA. In 1993, it was classified as inactive drug substance (Status I, Type II) and in 1995 the FDA studied the manufacturing procedures of Zotepine tablets in Germany, but the status remained inactive.[9] When the analysis of antipsychotics was retaken in 2016 by the FDA, zotepine did not reach the threshold effect to be further studied.[10]. In the EMA, by 2015 it was under pharmacovigilance studies for the potential treatment of acute renal failure.[11]

Structure
Thumb
Synonyms
Not Available
International/Other Brands
Losizopilon / Zoleptil
Categories
UNII
U29O83JAZW
CAS number
26615-21-4
Weight
Average: 331.86
Monoisotopic: 331.0797631
Chemical Formula
C18H18ClNOS
InChI Key
HDOZVRUNCMBHFH-UHFFFAOYSA-N
InChI
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
IUPAC Name
[2-({6-chloro-2-thiatricyclo[9.4.0.0³,⁸]pentadeca-1(15),3,5,7,9,11,13-heptaen-9-yl}oxy)ethyl]dimethylamine
SMILES
CN(C)CCOC1=CC2=CC=CC=C2SC2=CC=C(Cl)C=C12

Pharmacology

Indication

Zotepine, like other atypical antipsychotics, is considered as the first-line treatment in newly diagnosed schizophrenia. It is usually thought to be an option of choice for managing acute schizophrenic episodes when discussion with the patient is not possible. Zotepine, as an atypical antipsychotic, is used in patients who are suffering unacceptable side effects from conventional antipsychotics or in relapse patients that were inadequately controlled.[7]

It is important to consider that the indications stated above are related to atypical antipsychotics, that zotepine is not currently FDA, Canada or EMA approved and that studies have not shown any additional benefit when compared with other approved atypical antipsychotics.[2]

Schizophrenia is a chronic and severe mental disorder that affects how a person thinks, feels and behaves. It is usually marked for a loose reality perspective delineated by hallucinations, delusions and thought and movement disorders.[12]

Pharmacodynamics

In preclinical studies, zotepine is characterized by the presence of a strong antiserotonergic activity when compared with other neuroleptic drugs. It has also been reported to present elevations in the seizure threshold in the amygdaloid nucleus.[1] When zotepine's effects were analyzed by electroencephalography, it was noted a typical response of a low-potency neuroleptics of the sedative type. Administration of zotepine has shown improvements in numerical movements and complex reaction. These effects tend to be accompanied by increases in pulse rate, increase in prolactin levels and some typical neuroleptic side effects.[3, 4]

Mechanism of action

Zotepine is a dopamine antagonist that has a high affinity for D1- and D2-like receptors. It presents a strong antagonism for several serotonin receptors, such as 5-HT2a, 5-HT2c, 5-HT6 and 5-HT7. Zotepine activities are also related to the inhibition of noradrenaline reuptake and serotonergic activity. All these effects allow zotepine to improve the negative and cognitive symptoms of schizophrenia.[8]

TargetActionsOrganism
AD(1) dopamine receptor
antagonist
Human
AD(2) dopamine receptor
antagonist
Human
A5-hydroxytryptamine receptor 2A
antagonist
Human
U5-hydroxytryptamine receptor 6
antagonist
Human
A5-hydroxytryptamine receptor 7
antagonist
Human
ASodium-dependent noradrenaline transporter
antagonist
Human
ASodium-dependent serotonin transporter
antagonist
Human
Absorption

Preclinical pharmacokinetic studies have shown a dose-dependent increase in plasma levels with a tmax between 2-4 hours and Cmax from 6.9-19.6 ng/ml when administered in a dose of 25-100 mg of zotepine. The maximum concentration peaks and slow declines thereafter.[4] When administered orally in preclinical studies, zotepine was proven to be absorbed rapidly and almost completely from the gastrointestinal tract.The unchanged drug and metabolites are rapidly distributed to the tissues.[5]

Volume of distribution

The apparent volume of distribution of zotepine is 109 L/kg.[6]

Protein binding

Plasma protein binding of zotepine and its major active metabolite norzotepine account for 97% of the administered dose.[13]

Metabolism

Zotepine is well metabolized in the body, it actually undergoes extensive first-pass metabolism to the metabolite norzotepine and several inactive metabolites. The main enzymes involved in zotepine metabolism are CYP1A2 and CYP3A4.[13] Some of the main metabolic pathways include N-demethylation and oxygenation of N or S atoms, hydroxylation of the aromatic ring and consecutive conjugation.[5]

Route of elimination

Only small amounts of the unchanged zotepine are excreted in the urine and fecal excretion through the bile is the main route of elimination of both the unchanged drug and its metabolites.[5]

Half life

The half-life of zotepine is reported to be of 21 hours.[6]

Clearance

The apparent oral clearance of zotepine is 4.6 mg/h.kg.[6]

Toxicity

The use of zotepine has been vastly related to ongoing extrapyramidal side effects and it has been reported to be poorly tolerated by the patients.[1, 2]

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
2,5-Dimethoxy-4-ethylamphetamineZotepine may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylamphetamine.Experimental, Illicit
2,5-Dimethoxy-4-ethylthioamphetamineZotepine may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylthioamphetamine.Experimental
3,4-MethylenedioxyamphetamineZotepine may decrease the stimulatory activities of 3,4-Methylenedioxyamphetamine.Experimental, Illicit
4-Bromo-2,5-dimethoxyamphetamineZotepine may decrease the stimulatory activities of 4-Bromo-2,5-dimethoxyamphetamine.Experimental, Illicit
7-NitroindazoleThe risk or severity of adverse effects can be increased when 7-Nitroindazole is combined with Zotepine.Experimental
AbirateroneThe serum concentration of Zotepine can be increased when it is combined with Abiraterone.Approved
AcepromazineThe risk or severity of adverse effects can be increased when Acepromazine is combined with Zotepine.Approved, Vet Approved
AceprometazineThe risk or severity of adverse effects can be increased when Aceprometazine is combined with Zotepine.Approved
Acetyl sulfisoxazoleThe metabolism of Zotepine can be decreased when combined with Acetyl sulfisoxazole.Approved, Vet Approved
AdipiplonThe risk or severity of adverse effects can be increased when Adipiplon is combined with Zotepine.Investigational
AgomelatineThe risk or severity of adverse effects can be increased when Agomelatine is combined with Zotepine.Approved, Investigational
AlaproclateThe risk or severity of adverse effects can be increased when Zotepine is combined with Alaproclate.Experimental
AlfaxaloneThe risk or severity of adverse effects can be increased when Zotepine is combined with Alfaxalone.Vet Approved
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Zotepine.Approved, Illicit
AllopregnanoloneThe risk or severity of adverse effects can be increased when Zotepine is combined with Allopregnanolone.Investigational
AlmotriptanThe risk or severity of adverse effects can be increased when Almotriptan is combined with Zotepine.Approved, Investigational
AlphacetylmethadolThe risk or severity of adverse effects can be increased when Alphacetylmethadol is combined with Zotepine.Experimental, Illicit
AlphaprodineThe risk or severity of adverse effects can be increased when Zotepine is combined with Alphaprodine.Illicit
AlprazolamThe risk or severity of adverse effects can be increased when Alprazolam is combined with Zotepine.Approved, Illicit, Investigational
AmantadineThe therapeutic efficacy of Amantadine can be decreased when used in combination with Zotepine.Approved
AmiodaroneThe metabolism of Zotepine can be decreased when combined with Amiodarone.Approved, Investigational
AmisulprideZotepine may increase the antipsychotic activities of Amisulpride.Approved, Investigational
AmitriptylineThe risk or severity of adverse effects can be increased when Amitriptyline is combined with Zotepine.Approved
AmobarbitalThe risk or severity of adverse effects can be increased when Amobarbital is combined with Zotepine.Approved, Illicit
AmoxapineThe risk or severity of adverse effects can be increased when Amoxapine is combined with Zotepine.Approved
AmperozideThe risk or severity of adverse effects can be increased when Amperozide is combined with Zotepine.Experimental
AmphetamineZotepine may decrease the stimulatory activities of Amphetamine.Approved, Illicit, Investigational
ApalutamideThe serum concentration of Zotepine can be decreased when it is combined with Apalutamide.Approved, Investigational
ApomorphineThe therapeutic efficacy of Apomorphine can be decreased when used in combination with Zotepine.Approved, Investigational
AprepitantThe serum concentration of Zotepine can be increased when it is combined with Aprepitant.Approved, Investigational
AripiprazoleThe risk or severity of adverse effects can be increased when Aripiprazole is combined with Zotepine.Approved, Investigational
ArticaineThe risk or severity of adverse effects can be increased when Articaine is combined with Zotepine.Approved
AsenapineThe risk or severity of adverse effects can be increased when Asenapine is combined with Zotepine.Approved
AtazanavirThe metabolism of Zotepine can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Zotepine can be decreased when combined with Atomoxetine.Approved
AzaperoneThe risk or severity of adverse effects can be increased when Zotepine is combined with Azaperone.Investigational, Vet Approved
AzelastineZotepine may increase the central nervous system depressant (CNS depressant) activities of Azelastine.Approved
AzithromycinThe metabolism of Zotepine can be decreased when combined with Azithromycin.Approved
BaclofenThe risk or severity of adverse effects can be increased when Baclofen is combined with Zotepine.Approved
BarbitalThe risk or severity of adverse effects can be increased when Barbital is combined with Zotepine.Illicit
BenperidolThe risk or severity of adverse effects can be increased when Zotepine is combined with Benperidol.Approved, Investigational
BenzocaineThe risk or severity of adverse effects can be increased when Benzocaine is combined with Zotepine.Approved, Investigational
BenzphetamineZotepine may decrease the stimulatory activities of Benzphetamine.Approved, Illicit
Benzyl alcoholThe risk or severity of adverse effects can be increased when Benzyl alcohol is combined with Zotepine.Approved
BoceprevirThe metabolism of Zotepine can be decreased when combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Zotepine can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Zotepine can be decreased when it is combined with Bosentan.Approved, Investigational
BrexpiprazoleThe risk or severity of adverse effects can be increased when Brexpiprazole is combined with Zotepine.Approved, Investigational
BrimonidineBrimonidine may increase the central nervous system depressant (CNS depressant) activities of Zotepine.Approved
BromazepamThe risk or severity of adverse effects can be increased when Bromazepam is combined with Zotepine.Approved, Illicit, Investigational
BromisovalThe risk or severity of adverse effects can be increased when Zotepine is combined with Bromisoval.Experimental
BromocriptineThe therapeutic efficacy of Bromocriptine can be decreased when used in combination with Zotepine.Approved, Investigational
BromperidolThe risk or severity of adverse effects can be increased when Zotepine is combined with Bromperidol.Approved, Investigational
BrompheniramineThe risk or severity of adverse effects can be increased when Brompheniramine is combined with Zotepine.Approved
BrotizolamThe risk or severity of adverse effects can be increased when Brotizolam is combined with Zotepine.Approved, Investigational, Withdrawn
BupivacaineThe risk or severity of adverse effects can be increased when Bupivacaine is combined with Zotepine.Approved, Investigational
BuprenorphineZotepine may increase the central nervous system depressant (CNS depressant) activities of Buprenorphine.Approved, Illicit, Investigational, Vet Approved
BuspironeThe risk or severity of adverse effects can be increased when Buspirone is combined with Zotepine.Approved, Investigational
ButabarbitalThe risk or severity of adverse effects can be increased when Butabarbital is combined with Zotepine.Approved, Illicit
ButacaineThe risk or severity of adverse effects can be increased when Zotepine is combined with Butacaine.Vet Approved
ButalbitalThe risk or severity of adverse effects can be increased when Butalbital is combined with Zotepine.Approved, Illicit
ButambenThe risk or severity of adverse effects can be increased when Zotepine is combined with Butamben.Approved, Withdrawn
ButethalThe risk or severity of adverse effects can be increased when Butethal is combined with Zotepine.Approved, Illicit
ButorphanolThe risk or severity of adverse effects can be increased when Butorphanol is combined with Zotepine.Approved, Illicit, Vet Approved
CabergolineThe risk or severity of adverse effects can be increased when Cabergoline is combined with Zotepine.Approved
CaffeineThe metabolism of Zotepine can be decreased when combined with Caffeine.Approved
CanertinibThe risk or severity of adverse effects can be increased when Canertinib is combined with Zotepine.Investigational
CarbamazepineThe metabolism of Zotepine can be increased when combined with Carbamazepine.Approved, Investigational
CarbinoxamineThe risk or severity of adverse effects can be increased when Carbinoxamine is combined with Zotepine.Approved
CarfentanilThe risk or severity of adverse effects can be increased when Carfentanil is combined with Zotepine.Illicit, Investigational, Vet Approved
CarisoprodolThe risk or severity of adverse effects can be increased when Carisoprodol is combined with Zotepine.Approved
CeritinibThe serum concentration of Zotepine can be increased when it is combined with Ceritinib.Approved
CetirizineThe risk or severity of adverse effects can be increased when Cetirizine is combined with Zotepine.Approved
Chloral hydrateThe risk or severity of adverse effects can be increased when Chloral hydrate is combined with Zotepine.Approved, Illicit, Investigational, Vet Approved
ChlordiazepoxideThe risk or severity of adverse effects can be increased when Chlordiazepoxide is combined with Zotepine.Approved, Illicit, Investigational
ChlormezanoneThe risk or severity of adverse effects can be increased when Chlormezanone is combined with Zotepine.Approved, Investigational, Withdrawn
ChloroprocaineThe risk or severity of adverse effects can be increased when Chloroprocaine is combined with Zotepine.Approved
ChlorphenamineThe risk or severity of adverse effects can be increased when Chlorphenamine is combined with Zotepine.Approved
ChlorphentermineZotepine may decrease the stimulatory activities of Chlorphentermine.Illicit, Withdrawn
ChlorpromazineThe risk or severity of adverse effects can be increased when Chlorpromazine is combined with Zotepine.Approved, Investigational, Vet Approved
ChlorprothixeneThe risk or severity of adverse effects can be increased when Chlorprothixene is combined with Zotepine.Approved, Investigational, Withdrawn
ChlorzoxazoneThe risk or severity of adverse effects can be increased when Chlorzoxazone is combined with Zotepine.Approved
CinchocaineThe risk or severity of adverse effects can be increased when Cinchocaine is combined with Zotepine.Approved, Vet Approved
CitalopramThe risk or severity of adverse effects can be increased when Zotepine is combined with Citalopram.Approved
ClarithromycinThe metabolism of Zotepine can be decreased when combined with Clarithromycin.Approved
ClemastineThe risk or severity of adverse effects can be increased when Clemastine is combined with Zotepine.Approved, Investigational
ClidiniumThe risk or severity of adverse effects can be increased when Clidinium is combined with Zotepine.Approved
ClobazamThe risk or severity of adverse effects can be increased when Clobazam is combined with Zotepine.Approved, Illicit
clomethiazoleThe risk or severity of adverse effects can be increased when clomethiazole is combined with Zotepine.Investigational
ClomipramineThe risk or severity of adverse effects can be increased when Clomipramine is combined with Zotepine.Approved, Investigational, Vet Approved
ClonazepamThe risk or severity of adverse effects can be increased when Clonazepam is combined with Zotepine.Approved, Illicit
ClonidineThe risk or severity of adverse effects can be increased when Clonidine is combined with Zotepine.Approved
ClopenthixolThe risk or severity of adverse effects can be increased when Zotepine is combined with Clopenthixol.Experimental
ClorazepateThe risk or severity of adverse effects can be increased when Clorazepate is combined with Zotepine.Approved, Illicit
ClothiapineThe risk or severity of adverse effects can be increased when Zotepine is combined with Clothiapine.Experimental
ClotrimazoleThe metabolism of Zotepine can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe risk or severity of adverse effects can be increased when Clozapine is combined with Zotepine.Approved
CobicistatThe metabolism of Zotepine can be decreased when combined with Cobicistat.Approved
CocaineThe risk or severity of adverse effects can be increased when Cocaine is combined with Zotepine.Approved, Illicit
CodeineThe risk or severity of adverse effects can be increased when Codeine is combined with Zotepine.Approved, Illicit
ConivaptanThe serum concentration of Conivaptan can be increased when it is combined with Zotepine.Approved, Investigational
CrizotinibThe metabolism of Zotepine can be decreased when combined with Crizotinib.Approved
CurcuminThe metabolism of Zotepine can be decreased when combined with Curcumin.Approved, Investigational
CyclizineThe risk or severity of adverse effects can be increased when Cyclizine is combined with Zotepine.Approved
CyclobenzaprineThe risk or severity of adverse effects can be increased when Cyclobenzaprine is combined with Zotepine.Approved
CyclopropaneThe risk or severity of adverse effects can be increased when Zotepine is combined with Cyclopropane.Experimental
CyclosporineThe metabolism of Zotepine can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
CyproheptadineThe risk or severity of adverse effects can be increased when Cyproheptadine is combined with Zotepine.Approved
Cyproterone acetateThe serum concentration of Zotepine can be decreased when it is combined with Cyproterone acetate.Approved, Investigational
DabrafenibThe serum concentration of Zotepine can be decreased when it is combined with Dabrafenib.Approved, Investigational
DantroleneThe risk or severity of adverse effects can be increased when Dantrolene is combined with Zotepine.Approved, Investigational
DapiprazoleThe risk or severity of adverse effects can be increased when Dapiprazole is combined with Zotepine.Approved
DapoxetineThe risk or severity of adverse effects can be increased when Zotepine is combined with Dapoxetine.Investigational
DarunavirThe metabolism of Zotepine can be decreased when combined with Darunavir.Approved
DasatinibThe serum concentration of Zotepine can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Zotepine can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Zotepine can be decreased when combined with Delavirdine.Approved
DeramciclaneThe risk or severity of adverse effects can be increased when Deramciclane is combined with Zotepine.Investigational
DesfluraneThe risk or severity of adverse effects can be increased when Desflurane is combined with Zotepine.Approved
DesipramineThe risk or severity of adverse effects can be increased when Desipramine is combined with Zotepine.Approved, Investigational
DesloratadineThe risk or severity of adverse effects can be increased when Desloratadine is combined with Zotepine.Approved, Investigational
DesvenlafaxineThe risk or severity of adverse effects can be increased when Zotepine is combined with Desvenlafaxine.Approved, Investigational
DetomidineThe risk or severity of adverse effects can be increased when Zotepine is combined with Detomidine.Vet Approved
DeutetrabenazineThe risk or severity of adverse effects can be increased when Zotepine is combined with Deutetrabenazine.Approved, Investigational
DexbrompheniramineThe risk or severity of adverse effects can be increased when Dexbrompheniramine is combined with Zotepine.Approved
DexmedetomidineThe risk or severity of adverse effects can be increased when Dexmedetomidine is combined with Zotepine.Approved, Vet Approved
DextroamphetamineZotepine may decrease the stimulatory activities of Dextroamphetamine.Approved, Illicit
DextromethorphanThe risk or severity of adverse effects can be increased when Dextromethorphan is combined with Zotepine.Approved
DextromoramideThe risk or severity of adverse effects can be increased when Dextromoramide is combined with Zotepine.Experimental, Illicit
DextropropoxypheneThe risk or severity of adverse effects can be increased when Dextropropoxyphene is combined with Zotepine.Approved, Illicit, Investigational, Withdrawn
DezocineThe risk or severity of adverse effects can be increased when Dezocine is combined with Zotepine.Approved, Investigational
DiazepamThe risk or severity of adverse effects can be increased when Diazepam is combined with Zotepine.Approved, Illicit, Investigational, Vet Approved
Diethyl etherThe risk or severity of adverse effects can be increased when Zotepine is combined with Diethyl ether.Experimental
DiethylpropionZotepine may decrease the stimulatory activities of Diethylpropion.Approved, Illicit
DifenoxinThe risk or severity of adverse effects can be increased when Difenoxin is combined with Zotepine.Approved, Illicit
DihydrocodeineThe risk or severity of adverse effects can be increased when Dihydrocodeine is combined with Zotepine.Approved, Illicit
DihydroergotamineThe risk or severity of adverse effects can be increased when Dihydroergotamine is combined with Zotepine.Approved, Investigational
DihydroetorphineThe risk or severity of adverse effects can be increased when Dihydroetorphine is combined with Zotepine.Experimental, Illicit
DihydromorphineThe risk or severity of adverse effects can be increased when Dihydromorphine is combined with Zotepine.Experimental, Illicit
DiltiazemThe metabolism of Zotepine can be decreased when combined with Diltiazem.Approved, Investigational
DimenhydrinateThe risk or severity of adverse effects can be increased when Dimenhydrinate is combined with Zotepine.Approved
DiphenhydramineThe risk or severity of adverse effects can be increased when Diphenhydramine is combined with Zotepine.Approved, Investigational
DiphenoxylateThe risk or severity of adverse effects can be increased when Diphenoxylate is combined with Zotepine.Approved, Illicit
DixyrazineThe risk or severity of adverse effects can be increased when Zotepine is combined with Dixyrazine.Experimental
DoramectinThe risk or severity of adverse effects can be increased when Zotepine is combined with Doramectin.Vet Approved
DosulepinThe metabolism of Zotepine can be decreased when combined with Dosulepin.Approved
DoxepinThe risk or severity of adverse effects can be increased when Doxepin is combined with Zotepine.Approved, Investigational
DoxycyclineThe metabolism of Zotepine can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DoxylamineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of Zotepine.Approved, Vet Approved
DPDPEThe risk or severity of adverse effects can be increased when DPDPE is combined with Zotepine.Experimental
DronabinolDronabinol may increase the central nervous system depressant (CNS depressant) activities of Zotepine.Approved, Illicit
DronedaroneThe metabolism of Zotepine can be decreased when combined with Dronedarone.Approved
DroperidolDroperidol may increase the central nervous system depressant (CNS depressant) activities of Zotepine.Approved, Vet Approved
DrotebanolThe risk or severity of adverse effects can be increased when Drotebanol is combined with Zotepine.Experimental, Illicit
DuloxetineThe risk or severity of adverse effects can be increased when Zotepine is combined with Duloxetine.Approved
DyclonineThe risk or severity of adverse effects can be increased when Dyclonine is combined with Zotepine.Approved
EcgonineThe risk or severity of adverse effects can be increased when Ecgonine is combined with Zotepine.Experimental, Illicit
EcopipamThe risk or severity of adverse effects can be increased when Zotepine is combined with Ecopipam.Investigational
EfavirenzThe risk or severity of adverse effects can be increased when Efavirenz is combined with Zotepine.Approved, Investigational
EletriptanThe risk or severity of adverse effects can be increased when Eletriptan is combined with Zotepine.Approved, Investigational
EltanoloneThe risk or severity of adverse effects can be increased when Zotepine is combined with Eltanolone.Investigational
EnfluraneThe risk or severity of adverse effects can be increased when Enflurane is combined with Zotepine.Approved, Investigational, Vet Approved
EntacaponeThe risk or severity of adverse effects can be increased when Entacapone is combined with Zotepine.Approved, Investigational
EnzalutamideThe serum concentration of Zotepine can be decreased when it is combined with Enzalutamide.Approved
Ergoloid mesylateThe risk or severity of adverse effects can be increased when Ergoloid mesylate is combined with Zotepine.Approved
ErgonovineThe risk or severity of adverse effects can be increased when Ergonovine is combined with Zotepine.Approved
ErgotamineThe risk or severity of adverse effects can be increased when Ergotamine is combined with Zotepine.Approved
ErythromycinThe metabolism of Zotepine can be decreased when combined with Erythromycin.Approved, Investigational, Vet Approved
EscitalopramThe risk or severity of adverse effects can be increased when Zotepine is combined with Escitalopram.Approved, Investigational
EstazolamThe risk or severity of adverse effects can be increased when Estazolam is combined with Zotepine.Approved, Illicit
EszopicloneThe risk or severity of adverse effects can be increased when Eszopiclone is combined with Zotepine.Approved, Investigational
EthanolZotepine may increase the central nervous system depressant (CNS depressant) activities of Ethanol.Approved
EthchlorvynolThe risk or severity of adverse effects can be increased when Ethchlorvynol is combined with Zotepine.Approved, Illicit, Withdrawn
EthosuximideThe risk or severity of adverse effects can be increased when Ethosuximide is combined with Zotepine.Approved
EthotoinThe risk or severity of adverse effects can be increased when Ethotoin is combined with Zotepine.Approved
Ethyl carbamateThe risk or severity of adverse effects can be increased when Ethyl carbamate is combined with Zotepine.Withdrawn
Ethyl chlorideThe risk or severity of adverse effects can be increased when Zotepine is combined with Ethyl chloride.Approved, Experimental, Investigational
Ethyl loflazepateThe risk or severity of adverse effects can be increased when Ethyl loflazepate is combined with Zotepine.Approved, Illicit
EthylmorphineThe risk or severity of adverse effects can be increased when Ethylmorphine is combined with Zotepine.Approved, Illicit
EtidocaineThe risk or severity of adverse effects can be increased when Etidocaine is combined with Zotepine.Approved
EtifoxineThe risk or severity of adverse effects can be increased when Etifoxine is combined with Zotepine.Investigational, Withdrawn
EtizolamThe risk or severity of adverse effects can be increased when Etizolam is combined with Zotepine.Approved
EtomidateThe risk or severity of adverse effects can be increased when Etomidate is combined with Zotepine.Approved
EtoperidoneThe risk or severity of adverse effects can be increased when Zotepine is combined with Etoperidone.Withdrawn
EtorphineThe risk or severity of adverse effects can be increased when Etorphine is combined with Zotepine.Illicit, Vet Approved
EzogabineThe risk or severity of adverse effects can be increased when Ezogabine is combined with Zotepine.Approved, Investigational
FelbamateThe risk or severity of adverse effects can be increased when Felbamate is combined with Zotepine.Approved
FencamfamineThe risk or severity of adverse effects can be increased when Fencamfamine is combined with Zotepine.Approved, Illicit, Withdrawn
FentanylThe risk or severity of adverse effects can be increased when Fentanyl is combined with Zotepine.Approved, Illicit, Investigational, Vet Approved
FexofenadineThe risk or severity of adverse effects can be increased when Fexofenadine is combined with Zotepine.Approved, Investigational
FlibanserinThe risk or severity of adverse effects can be increased when Flibanserin is combined with Zotepine.Approved, Investigational
FluanisoneThe risk or severity of adverse effects can be increased when Zotepine is combined with Fluanisone.Experimental
FluconazoleThe metabolism of Zotepine can be decreased when combined with Fluconazole.Approved, Investigational
FludiazepamThe risk or severity of adverse effects can be increased when Fludiazepam is combined with Zotepine.Approved, Illicit
FlunarizineThe risk or severity of adverse effects can be increased when Flunarizine is combined with Zotepine.Approved
FlunitrazepamThe risk or severity of adverse effects can be increased when Flunitrazepam is combined with Zotepine.Approved, Illicit
FluoxetineThe risk or severity of adverse effects can be increased when Zotepine is combined with Fluoxetine.Approved, Vet Approved
FlupentixolThe risk or severity of adverse effects can be increased when Flupentixol is combined with Zotepine.Approved, Investigational, Withdrawn
FluphenazineThe risk or severity of adverse effects can be increased when Fluphenazine is combined with Zotepine.Approved
FlurazepamThe risk or severity of adverse effects can be increased when Flurazepam is combined with Zotepine.Approved, Illicit, Investigational
FluspirileneThe risk or severity of adverse effects can be increased when Fluspirilene is combined with Zotepine.Approved, Investigational
Fluticasone propionateThe risk or severity of adverse effects can be increased when Fluticasone propionate is combined with Zotepine.Approved
FluvoxamineThe metabolism of Zotepine can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Zotepine can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Zotepine can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Zotepine can be increased when combined with Fosphenytoin.Approved, Investigational
FospropofolThe risk or severity of adverse effects can be increased when Fospropofol is combined with Zotepine.Approved, Illicit, Investigational
FrovatriptanThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Zotepine.Approved, Investigational
Fusidic AcidThe serum concentration of Zotepine can be increased when it is combined with Fusidic Acid.Approved, Investigational
GabapentinThe risk or severity of adverse effects can be increased when Gabapentin is combined with Zotepine.Approved, Investigational
Gabapentin EnacarbilThe risk or severity of adverse effects can be increased when Gabapentin Enacarbil is combined with Zotepine.Approved, Investigational
Gamma Hydroxybutyric AcidThe risk or severity of adverse effects can be increased when Gamma Hydroxybutyric Acid is combined with Zotepine.Approved, Illicit, Investigational
GepefrineZotepine may decrease the stimulatory activities of Gepefrine.Experimental
GepironeThe risk or severity of adverse effects can be increased when Zotepine is combined with Gepirone.Investigational
GlutethimideThe risk or severity of adverse effects can be increased when Glutethimide is combined with Zotepine.Approved, Illicit
GuanfacineThe risk or severity of adverse effects can be increased when Guanfacine is combined with Zotepine.Approved, Investigational
HalazepamThe risk or severity of adverse effects can be increased when Halazepam is combined with Zotepine.Approved, Illicit, Withdrawn
HaloperidolThe risk or severity of adverse effects can be increased when Haloperidol is combined with Zotepine.Approved
HalothaneThe risk or severity of adverse effects can be increased when Halothane is combined with Zotepine.Approved, Vet Approved
HeroinThe risk or severity of adverse effects can be increased when Heroin is combined with Zotepine.Approved, Illicit, Investigational
HexobarbitalThe risk or severity of adverse effects can be increased when Hexobarbital is combined with Zotepine.Approved
HydrocodoneZotepine may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.Approved, Illicit
HydromorphoneThe risk or severity of adverse effects can be increased when Hydromorphone is combined with Zotepine.Approved, Illicit
HydroxyamphetamineZotepine may decrease the stimulatory activities of Hydroxyamphetamine.Approved
HydroxyzineHydroxyzine may increase the central nervous system depressant (CNS depressant) activities of Zotepine.Approved
IdelalisibThe metabolism of Zotepine can be decreased when combined with Idelalisib.Approved
IloperidoneThe risk or severity of adverse effects can be increased when Iloperidone is combined with Zotepine.Approved
ImatinibThe metabolism of Zotepine can be decreased when combined with Imatinib.Approved
ImipramineThe risk or severity of adverse effects can be increased when Imipramine is combined with Zotepine.Approved
IndalpineThe risk or severity of adverse effects can be increased when Zotepine is combined with Indalpine.Investigational, Withdrawn
IndinavirThe metabolism of Zotepine can be decreased when combined with Indinavir.Approved
IndiplonThe risk or severity of adverse effects can be increased when Zotepine is combined with Indiplon.Investigational
Iofetamine I-123Zotepine may decrease the stimulatory activities of Iofetamine I-123.Approved
IsavuconazoleThe serum concentration of Zotepine can be increased when it is combined with Isavuconazole.Approved, Investigational
IsavuconazoniumThe metabolism of Zotepine can be decreased when combined with Isavuconazonium.Approved, Investigational
IsocarboxazidThe therapeutic efficacy of Zotepine can be increased when used in combination with Isocarboxazid.Approved
IsofluraneThe risk or severity of adverse effects can be increased when Isoflurane is combined with Zotepine.Approved, Vet Approved
IsradipineThe metabolism of Zotepine can be decreased when combined with Isradipine.Approved, Investigational
ItraconazoleThe metabolism of Zotepine can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Zotepine can be increased when it is combined with Ivacaftor.Approved
KetamineThe risk or severity of adverse effects can be increased when Ketamine is combined with Zotepine.Approved, Vet Approved
KetazolamThe risk or severity of adverse effects can be increased when Ketazolam is combined with Zotepine.Approved
KetobemidoneThe risk or severity of adverse effects can be increased when Ketobemidone is combined with Zotepine.Approved, Investigational
KetoconazoleThe metabolism of Zotepine can be decreased when combined with Ketoconazole.Approved, Investigational
LamotrigineThe risk or severity of adverse effects can be increased when Lamotrigine is combined with Zotepine.Approved, Investigational
LevetiracetamThe risk or severity of adverse effects can be increased when Levetiracetam is combined with Zotepine.Approved, Investigational
LevobupivacaineThe risk or severity of adverse effects can be increased when Levobupivacaine is combined with Zotepine.Approved, Investigational
LevocabastineThe risk or severity of adverse effects can be increased when Zotepine is combined with Levocabastine.Approved, Investigational
LevocetirizineThe risk or severity of adverse effects can be increased when Levocetirizine is combined with Zotepine.Approved
LevodopaThe therapeutic efficacy of Levodopa can be decreased when used in combination with Zotepine.Approved
Levomethadyl AcetateThe risk or severity of adverse effects can be increased when Levomethadyl Acetate is combined with Zotepine.Approved, Investigational
LevomilnacipranThe risk or severity of adverse effects can be increased when Zotepine is combined with Levomilnacipran.Approved, Investigational
LevorphanolThe risk or severity of adverse effects can be increased when Levorphanol is combined with Zotepine.Approved
LidocaineThe risk or severity of adverse effects can be increased when Lidocaine is combined with Zotepine.Approved, Vet Approved
LinezolidThe risk or severity of adverse effects can be increased when Linezolid is combined with Zotepine.Approved, Investigational
LisdexamfetamineZotepine may decrease the stimulatory activities of Lisdexamfetamine.Approved, Investigational
LithiumLithium may increase the neurotoxic activities of Zotepine.Approved
LobeglitazoneThe metabolism of Zotepine can be decreased when combined with Lobeglitazone.Approved, Investigational
LofentanilThe risk or severity of adverse effects can be increased when Lofentanil is combined with Zotepine.Illicit
LofexidineThe therapeutic efficacy of Zotepine can be increased when used in combination with Lofexidine.Approved, Investigational
LopinavirThe metabolism of Zotepine can be decreased when combined with Lopinavir.Approved
LoprazolamThe risk or severity of adverse effects can be increased when Zotepine is combined with Loprazolam.Experimental
LoratadineThe risk or severity of adverse effects can be increased when Loratadine is combined with Zotepine.Approved, Investigational
LorazepamThe risk or severity of adverse effects can be increased when Lorazepam is combined with Zotepine.Approved
LorcaserinThe risk or severity of adverse effects can be increased when Lorcaserin is combined with Zotepine.Approved
LormetazepamThe risk or severity of adverse effects can be increased when Zotepine is combined with Lormetazepam.Approved
LorpiprazoleThe serum concentration of Zotepine can be increased when it is combined with Lorpiprazole.Approved
LovastatinThe metabolism of Zotepine can be decreased when combined with Lovastatin.Approved, Investigational
LoxapineThe risk or severity of adverse effects can be increased when Loxapine is combined with Zotepine.Approved
LuliconazoleThe serum concentration of Zotepine can be increased when it is combined with Luliconazole.Approved
LumacaftorThe metabolism of Zotepine can be increased when combined with Lumacaftor.Approved
LurasidoneThe risk or severity of adverse effects can be increased when Lurasidone is combined with Zotepine.Approved, Investigational
Magnesium sulfateThe therapeutic efficacy of Zotepine can be increased when used in combination with Magnesium sulfate.Approved, Investigational, Vet Approved
MaprotilineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Zotepine.Approved, Investigational
MebicarThe risk or severity of adverse effects can be increased when Zotepine is combined with Mebicar.Experimental
MeclizineThe risk or severity of adverse effects can be increased when Meclizine is combined with Zotepine.Approved
MedazepamThe risk or severity of adverse effects can be increased when Zotepine is combined with Medazepam.Experimental
MedetomidineThe risk or severity of adverse effects can be increased when Zotepine is combined with Medetomidine.Vet Approved
MelatoninThe risk or severity of adverse effects can be increased when Melatonin is combined with Zotepine.Approved, Nutraceutical, Vet Approved
MelperoneThe risk or severity of adverse effects can be increased when Melperone is combined with Zotepine.Approved, Investigational
MephedroneZotepine may decrease the stimulatory activities of Mephedrone.Investigational
MephentermineZotepine may decrease the stimulatory activities of Mephentermine.Approved
MepivacaineThe risk or severity of adverse effects can be increased when Mepivacaine is combined with Zotepine.Approved, Vet Approved
MeprobamateThe risk or severity of adverse effects can be increased when Meprobamate is combined with Zotepine.Approved, Illicit
MeptazinolThe risk or severity of adverse effects can be increased when Zotepine is combined with Meptazinol.Experimental
MequitazineZotepine may increase the arrhythmogenic activities of Mequitazine.Approved
MesoridazineThe risk or severity of adverse effects can be increased when Mesoridazine is combined with Zotepine.Approved, Investigational
MetaxaloneThe risk or severity of adverse effects can be increased when Metaxalone is combined with Zotepine.Approved
MethadoneThe risk or severity of adverse effects can be increased when Methadone is combined with Zotepine.Approved
Methadyl AcetateThe risk or severity of adverse effects can be increased when Methadyl Acetate is combined with Zotepine.Approved, Illicit
MethamphetamineZotepine may decrease the stimulatory activities of Methamphetamine.Approved, Illicit
MethapyrileneThe risk or severity of adverse effects can be increased when Methapyrilene is combined with Zotepine.Withdrawn
MethaqualoneThe risk or severity of adverse effects can be increased when Methaqualone is combined with Zotepine.Illicit, Withdrawn
MethocarbamolThe risk or severity of adverse effects can be increased when Methocarbamol is combined with Zotepine.Approved, Vet Approved
MethohexitalThe risk or severity of adverse effects can be increased when Methohexital is combined with Zotepine.Approved
MethotrimeprazineZotepine may increase the central nervous system depressant (CNS depressant) activities of Methotrimeprazine.Approved, Investigational
MethoxyfluraneThe risk or severity of adverse effects can be increased when Methoxyflurane is combined with Zotepine.Approved, Investigational, Vet Approved
MethoxyphenamineZotepine may decrease the stimulatory activities of Methoxyphenamine.Experimental
MethsuximideThe risk or severity of adverse effects can be increased when Methsuximide is combined with Zotepine.Approved
MethylecgonineThe risk or severity of adverse effects can be increased when Methylecgonine is combined with Zotepine.Experimental
MethylphenidateThe risk or severity of adverse effects can be increased when Zotepine is combined with Methylphenidate.Approved, Investigational
MethylphenobarbitalThe risk or severity of adverse effects can be increased when Methylphenobarbital is combined with Zotepine.Approved
MetoclopramideThe risk or severity of adverse effects can be increased when Metoclopramide is combined with Zotepine.Approved, Investigational
MetyrosineZotepine may increase the sedative activities of Metyrosine.Approved
MexiletineThe metabolism of Zotepine can be decreased when combined with Mexiletine.Approved, Investigational
MidazolamThe risk or severity of adverse effects can be increased when Midazolam is combined with Zotepine.Approved, Illicit
MidomafetamineZotepine may decrease the stimulatory activities of Midomafetamine.Experimental, Illicit, Investigational
MidostaurinThe metabolism of Zotepine can be decreased when combined with Midostaurin.Approved, Investigational
MifepristoneThe serum concentration of Zotepine can be increased when it is combined with Mifepristone.Approved, Investigational
MilnacipranThe risk or severity of adverse effects can be increased when Zotepine is combined with Milnacipran.Approved, Investigational
MinocyclineMinocycline may increase the central nervous system depressant (CNS depressant) activities of Zotepine.Approved, Investigational
MirtazapineZotepine may increase the central nervous system depressant (CNS depressant) activities of Mirtazapine.Approved
MitotaneThe serum concentration of Zotepine can be decreased when it is combined with Mitotane.Approved
MMDAZotepine may decrease the stimulatory activities of MMDA.Experimental, Illicit
MoclobemideThe risk or severity of adverse effects can be increased when Moclobemide is combined with Zotepine.Approved, Investigational
MolindoneThe risk or severity of adverse effects can be increased when Molindone is combined with Zotepine.Approved
MorphineThe risk or severity of adverse effects can be increased when Morphine is combined with Zotepine.Approved, Investigational
NabiloneNabilone may increase the central nervous system depressant (CNS depressant) activities of Zotepine.Approved, Investigational
NalbuphineThe risk or severity of adverse effects can be increased when Nalbuphine is combined with Zotepine.Approved
NaratriptanThe risk or severity of adverse effects can be increased when Naratriptan is combined with Zotepine.Approved, Investigational
NefazodoneThe metabolism of Zotepine can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Zotepine can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Zotepine can be increased when it is combined with Netupitant.Approved, Investigational
NevirapineThe metabolism of Zotepine can be increased when combined with Nevirapine.Approved
NilotinibThe metabolism of Zotepine can be decreased when combined with Nilotinib.Approved, Investigational
NitrazepamThe risk or severity of adverse effects can be increased when Nitrazepam is combined with Zotepine.Approved
Nitrous oxideThe risk or severity of adverse effects can be increased when Nitrous oxide is combined with Zotepine.Approved, Vet Approved
NordazepamThe risk or severity of adverse effects can be increased when Zotepine is combined with Nordazepam.Approved
NorfluraneThe risk or severity of adverse effects can be increased when Zotepine is combined with Norflurane.Approved, Investigational
NormethadoneThe risk or severity of adverse effects can be increased when Zotepine is combined with Normethadone.Approved, Illicit
NortriptylineThe risk or severity of adverse effects can be increased when Nortriptyline is combined with Zotepine.Approved
OlanzapineThe risk or severity of adverse effects can be increased when Olanzapine is combined with Zotepine.Approved, Investigational
OlaparibThe metabolism of Zotepine can be decreased when combined with Olaparib.Approved
OlopatadineThe risk or severity of adverse effects can be increased when Olopatadine is combined with Zotepine.Approved
OndansetronThe risk or severity of adverse effects can be increased when Ondansetron is combined with Zotepine.Approved
OpiumThe risk or severity of adverse effects can be increased when Zotepine is combined with Opium.Approved, Illicit
OrphenadrineZotepine may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.Approved
OsanetantThe risk or severity of adverse effects can be increased when Osanetant is combined with Zotepine.Investigational
OsimertinibThe serum concentration of Zotepine can be increased when it is combined with Osimertinib.Approved
OxazepamThe risk or severity of adverse effects can be increased when Oxazepam is combined with Zotepine.Approved
OxprenololThe risk or severity of adverse effects can be increased when Oxprenolol is combined with Zotepine.Approved
OxybuprocaineThe risk or severity of adverse effects can be increased when Oxybuprocaine is combined with Zotepine.Approved, Investigational
OxycodoneThe risk or severity of adverse effects can be increased when Oxycodone is combined with Zotepine.Approved, Illicit, Investigational
OxymorphoneThe risk or severity of adverse effects can be increased when Oxymorphone is combined with Zotepine.Approved, Investigational, Vet Approved
PalbociclibThe serum concentration of Zotepine can be increased when it is combined with Palbociclib.Approved, Investigational
PaliperidoneThe risk or severity of adverse effects can be increased when Paliperidone is combined with Zotepine.Approved
ParaldehydeZotepine may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.Approved, Investigational
ParoxetineThe risk or severity of adverse effects can be increased when Zotepine is combined with Paroxetine.Approved, Investigational
Peginterferon alfa-2bThe serum concentration of Zotepine can be increased when it is combined with Peginterferon alfa-2b.Approved
PenfluridolThe risk or severity of adverse effects can be increased when Zotepine is combined with Penfluridol.Experimental
PentazocineThe risk or severity of adverse effects can be increased when Pentazocine is combined with Zotepine.Approved, Vet Approved
PentobarbitalThe metabolism of Zotepine can be increased when combined with Pentobarbital.Approved, Investigational, Vet Approved
PerampanelPerampanel may increase the central nervous system depressant (CNS depressant) activities of Zotepine.Approved
PerazineThe risk or severity of adverse effects can be increased when Zotepine is combined with Perazine.Approved, Investigational
PerospironeThe risk or severity of adverse effects can be increased when Perospirone is combined with Zotepine.Approved
PerphenazineThe risk or severity of adverse effects can be increased when Perphenazine is combined with Zotepine.Approved
PethidineThe risk or severity of adverse effects can be increased when Pethidine is combined with Zotepine.Approved
PhenazocineThe risk or severity of adverse effects can be increased when Zotepine is combined with Phenazocine.Experimental
PhenelzineThe risk or severity of adverse effects can be increased when Phenelzine is combined with Zotepine.Approved
PhenibutThe risk or severity of adverse effects can be increased when Zotepine is combined with Phenibut.Experimental
PhenobarbitalThe metabolism of Zotepine can be increased when combined with Phenobarbital.Approved, Investigational
PhenoperidineThe risk or severity of adverse effects can be increased when Zotepine is combined with Phenoperidine.Experimental
PhenoxyethanolThe risk or severity of adverse effects can be increased when Zotepine is combined with Phenoxyethanol.Approved
PhentermineZotepine may decrease the stimulatory activities of Phentermine.Approved, Illicit
PhenytoinThe metabolism of Zotepine can be increased when combined with Phenytoin.Approved, Vet Approved
PimozideThe risk or severity of adverse effects can be increased when Pimozide is combined with Zotepine.Approved
PipamperoneThe risk or severity of adverse effects can be increased when Zotepine is combined with Pipamperone.Approved, Investigational
PipotiazineThe risk or severity of adverse effects can be increased when Pipotiazine is combined with Zotepine.Approved, Investigational
PiribedilThe therapeutic efficacy of Piribedil can be decreased when used in combination with Zotepine.Investigational
PiritramideThe risk or severity of adverse effects can be increased when Zotepine is combined with Piritramide.Approved, Investigational
PitolisantThe serum concentration of Zotepine can be decreased when it is combined with Pitolisant.Approved, Investigational
PizotifenThe risk or severity of adverse effects can be increased when Pizotifen is combined with Zotepine.Approved
PomalidomideThe risk or severity of adverse effects can be increased when Pomalidomide is combined with Zotepine.Approved
PosaconazoleThe metabolism of Zotepine can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PramipexoleZotepine may increase the sedative activities of Pramipexole.Approved, Investigational
PramocaineThe risk or severity of adverse effects can be increased when Zotepine is combined with Pramocaine.Approved
PrazepamThe risk or severity of adverse effects can be increased when Prazepam is combined with Zotepine.Approved, Illicit
PregabalinThe therapeutic efficacy of Zotepine can be increased when used in combination with Pregabalin.Approved, Illicit, Investigational
PrilocaineThe risk or severity of adverse effects can be increased when Prilocaine is combined with Zotepine.Approved
PrimidoneThe metabolism of Zotepine can be increased when combined with Primidone.Approved, Vet Approved
ProcaineThe risk or severity of adverse effects can be increased when Procaine is combined with Zotepine.Approved, Investigational, Vet Approved
ProcarbazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Zotepine.Approved, Investigational
ProchlorperazineThe risk or severity of adverse effects can be increased when Prochlorperazine is combined with Zotepine.Approved, Vet Approved
PromazineThe risk or severity of adverse effects can be increased when Promazine is combined with Zotepine.Approved, Vet Approved
PromethazineThe risk or severity of adverse effects can be increased when Promethazine is combined with Zotepine.Approved, Investigational
PropanididThe risk or severity of adverse effects can be increased when Zotepine is combined with Propanidid.Experimental
ProparacaineThe risk or severity of adverse effects can be increased when Proparacaine is combined with Zotepine.Approved, Vet Approved
PropofolThe risk or severity of adverse effects can be increased when Propofol is combined with Zotepine.Approved, Investigational, Vet Approved
PropoxycaineThe risk or severity of adverse effects can be increased when Zotepine is combined with Propoxycaine.Approved
ProtriptylineThe risk or severity of adverse effects can be increased when Protriptyline is combined with Zotepine.Approved
ProxibarbalThe risk or severity of adverse effects can be increased when Zotepine is combined with Proxibarbal.Experimental
PSD502The risk or severity of adverse effects can be increased when PSD502 is combined with Zotepine.Investigational
PseudoephedrineZotepine may decrease the stimulatory activities of Pseudoephedrine.Approved
QuazepamThe risk or severity of adverse effects can be increased when Quazepam is combined with Zotepine.Approved, Illicit
QuetiapineThe risk or severity of adverse effects can be increased when Quetiapine is combined with Zotepine.Approved
QuinagolideThe therapeutic efficacy of Quinagolide can be decreased when used in combination with Zotepine.Approved, Investigational
QuinisocaineThe risk or severity of adverse effects can be increased when Zotepine is combined with Quinisocaine.Experimental
RacloprideThe risk or severity of adverse effects can be increased when Zotepine is combined with Raclopride.Investigational
RamelteonThe risk or severity of adverse effects can be increased when Ramelteon is combined with Zotepine.Approved, Investigational
RanolazineThe metabolism of Zotepine can be decreased when combined with Ranolazine.Approved, Investigational
RasagilineThe risk or severity of adverse effects can be increased when Rasagiline is combined with Zotepine.Approved
RemifentanilThe risk or severity of adverse effects can be increased when Remifentanil is combined with Zotepine.Approved
RemoxiprideThe risk or severity of adverse effects can be increased when Remoxipride is combined with Zotepine.Approved, Withdrawn
ReserpineThe risk or severity of adverse effects can be increased when Reserpine is combined with Zotepine.Approved, Investigational
RifabutinThe metabolism of Zotepine can be increased when combined with Rifabutin.Approved, Investigational
RifampicinThe metabolism of Zotepine can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Zotepine can be increased when combined with Rifapentine.Approved, Investigational
RisperidoneThe risk or severity of adverse effects can be increased when Risperidone is combined with Zotepine.Approved, Investigational
RitanserinThe risk or severity of adverse effects can be increased when Zotepine is combined with Ritanserin.Investigational
RitobegronZotepine may decrease the stimulatory activities of Ritobegron.Investigational
RizatriptanThe risk or severity of adverse effects can be increased when Rizatriptan is combined with Zotepine.Approved
RomifidineThe risk or severity of adverse effects can be increased when Zotepine is combined with Romifidine.Vet Approved
RopiniroleZotepine may increase the sedative activities of Ropinirole.Approved, Investigational
RopivacaineThe risk or severity of adverse effects can be increased when Ropivacaine is combined with Zotepine.Approved
RotigotineZotepine may increase the sedative activities of Rotigotine.Approved
RucaparibThe metabolism of Zotepine can be decreased when combined with Rucaparib.Approved, Investigational
RufinamideThe risk or severity of adverse effects can be increased when Rufinamide is combined with Zotepine.Approved
SaquinavirThe metabolism of Zotepine can be decreased when combined with Saquinavir.Approved, Investigational
SarilumabThe therapeutic efficacy of Zotepine can be decreased when used in combination with Sarilumab.Approved, Investigational
ScopolamineThe risk or severity of adverse effects can be increased when Scopolamine is combined with Zotepine.Approved, Investigational
SecobarbitalThe risk or severity of adverse effects can be increased when Secobarbital is combined with Zotepine.Approved, Vet Approved
SelegilineThe risk or severity of adverse effects can be increased when Selegiline is combined with Zotepine.Approved, Investigational, Vet Approved
SepranoloneThe risk or severity of adverse effects can be increased when Zotepine is combined with Sepranolone.Investigational
SertindoleThe risk or severity of adverse effects can be increased when Sertindole is combined with Zotepine.Approved, Investigational, Withdrawn
SertralineThe risk or severity of adverse effects can be increased when Zotepine is combined with Sertraline.Approved
SevofluraneThe risk or severity of adverse effects can be increased when Sevoflurane is combined with Zotepine.Approved, Vet Approved
SildenafilThe metabolism of Zotepine can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Zotepine can be decreased when it is combined with Siltuximab.Approved, Investigational
SimeprevirThe serum concentration of Zotepine can be increased when it is combined with Simeprevir.Approved
Sodium oxybateSodium oxybate may increase the central nervous system depressant (CNS depressant) activities of Zotepine.Approved
St. John's WortThe serum concentration of Zotepine can be decreased when it is combined with St. John's Wort.Approved, Investigational, Nutraceutical
StiripentolThe serum concentration of Zotepine can be increased when it is combined with Stiripentol.Approved
SufentanilThe risk or severity of adverse effects can be increased when Sufentanil is combined with Zotepine.Approved, Investigational
SulfisoxazoleThe metabolism of Zotepine can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
SulpirideZotepine may increase the antipsychotic activities of Sulpiride.Approved, Investigational
SultoprideThe risk or severity of adverse effects can be increased when Zotepine is combined with Sultopride.Experimental
SumatriptanThe risk or severity of adverse effects can be increased when Sumatriptan is combined with Zotepine.Approved, Investigational
SuvorexantZotepine may increase the central nervous system depressant (CNS depressant) activities of Suvorexant.Approved, Investigational
TandospironeThe risk or severity of adverse effects can be increased when Zotepine is combined with Tandospirone.Investigational
TapentadolTapentadol may increase the central nervous system depressant (CNS depressant) activities of Zotepine.Approved
TasimelteonThe risk or severity of adverse effects can be increased when Tasimelteon is combined with Zotepine.Approved, Investigational
Tedizolid PhosphateThe risk or severity of adverse effects can be increased when Tedizolid Phosphate is combined with Zotepine.Approved
TelaprevirThe metabolism of Zotepine can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Zotepine can be decreased when combined with Telithromycin.Approved
TemazepamThe risk or severity of adverse effects can be increased when Temazepam is combined with Zotepine.Approved, Investigational
Tenofovir disoproxilThe metabolism of Zotepine can be decreased when combined with Tenofovir disoproxil.Approved, Investigational
TeriflunomideThe serum concentration of Zotepine can be decreased when it is combined with Teriflunomide.Approved
TetrabenazineThe risk or severity of adverse effects can be increased when Tetrabenazine is combined with Zotepine.Approved, Investigational
TetracaineThe risk or severity of adverse effects can be increased when Tetracaine is combined with Zotepine.Approved, Vet Approved
TetrahydropalmatineThe risk or severity of adverse effects can be increased when Zotepine is combined with Tetrahydropalmatine.Investigational
TetrodotoxinThe risk or severity of adverse effects can be increased when Tetrodotoxin is combined with Zotepine.Investigational
ThalidomideZotepine may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.Approved, Investigational, Withdrawn
TheophyllineThe metabolism of Zotepine can be decreased when combined with Theophylline.Approved
ThiamylalThe risk or severity of adverse effects can be increased when Thiamylal is combined with Zotepine.Approved, Vet Approved
ThiopentalThe risk or severity of adverse effects can be increased when Thiopental is combined with Zotepine.Approved, Vet Approved
ThioridazineThe risk or severity of adverse effects can be increased when Thioridazine is combined with Zotepine.Approved, Withdrawn
ThiothixeneThe risk or severity of adverse effects can be increased when Thiothixene is combined with Zotepine.Approved
TiagabineThe risk or severity of adverse effects can be increased when Tiagabine is combined with Zotepine.Approved, Investigational
TiaprideThe risk or severity of adverse effects can be increased when Zotepine is combined with Tiapride.Approved, Investigational
TiclopidineThe metabolism of Zotepine can be decreased when combined with Ticlopidine.Approved
TiletamineThe risk or severity of adverse effects can be increased when Zotepine is combined with Tiletamine.Vet Approved
TilidineThe risk or severity of adverse effects can be increased when Zotepine is combined with Tilidine.Experimental
TizanidineThe risk or severity of adverse effects can be increased when Tizanidine is combined with Zotepine.Approved, Investigational
TocilizumabThe serum concentration of Zotepine can be decreased when it is combined with Tocilizumab.Approved
TolcaponeThe risk or severity of adverse effects can be increased when Tolcapone is combined with Zotepine.Approved, Withdrawn
TopiramateThe risk or severity of adverse effects can be increased when Topiramate is combined with Zotepine.Approved
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Zotepine.Approved, Investigational
TranylcypromineThe risk or severity of adverse effects can be increased when Tranylcypromine is combined with Zotepine.Approved, Investigational
TrazodoneThe risk or severity of adverse effects can be increased when Trazodone is combined with Zotepine.Approved, Investigational
TriazolamThe risk or severity of adverse effects can be increased when Triazolam is combined with Zotepine.Approved, Investigational
Tricaine methanesulfonateThe risk or severity of adverse effects can be increased when Zotepine is combined with Tricaine methanesulfonate.Vet Approved
TrichloroethyleneThe risk or severity of adverse effects can be increased when Zotepine is combined with Trichloroethylene.Approved
TrifluoperazineThe risk or severity of adverse effects can be increased when Trifluoperazine is combined with Zotepine.Approved, Investigational
TrifluperidolThe risk or severity of adverse effects can be increased when Zotepine is combined with Trifluperidol.Experimental
TriflupromazineThe risk or severity of adverse effects can be increased when Triflupromazine is combined with Zotepine.Approved, Vet Approved
TrimipramineThe risk or severity of adverse effects can be increased when Trimipramine is combined with Zotepine.Approved
TriprolidineThe risk or severity of adverse effects can be increased when Triprolidine is combined with Zotepine.Approved
Valproic AcidThe risk or severity of adverse effects can be increased when Valproic Acid is combined with Zotepine.Approved, Investigational
VemurafenibThe risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Zotepine.Approved
VenlafaxineThe risk or severity of adverse effects can be increased when Zotepine is combined with Venlafaxine.Approved
VeraliprideThe risk or severity of adverse effects can be increased when Zotepine is combined with Veralipride.Experimental
VerapamilThe metabolism of Zotepine can be decreased when combined with Verapamil.Approved
VigabatrinThe risk or severity of adverse effects can be increased when Vigabatrin is combined with Zotepine.Approved
VilazodoneThe risk or severity of adverse effects can be increased when Vilazodone is combined with Zotepine.Approved
Vinyl etherThe risk or severity of adverse effects can be increased when Zotepine is combined with Vinyl ether.Experimental
VoriconazoleThe metabolism of Zotepine can be decreased when combined with Voriconazole.Approved, Investigational
VortioxetineThe risk or severity of adverse effects can be increased when Vortioxetine is combined with Zotepine.Approved, Investigational
XenonThe risk or severity of adverse effects can be increased when Zotepine is combined with Xenon.Experimental
XylazineThe risk or severity of adverse effects can be increased when Zotepine is combined with Xylazine.Vet Approved
ZaleplonThe risk or severity of adverse effects can be increased when Zaleplon is combined with Zotepine.Approved, Illicit, Investigational
ZiconotideThe risk or severity of adverse effects can be increased when Ziconotide is combined with Zotepine.Approved
ZimelidineThe risk or severity of adverse effects can be increased when Zotepine is combined with Zimelidine.Withdrawn
ZiprasidoneThe risk or severity of adverse effects can be increased when Ziprasidone is combined with Zotepine.Approved
ZolazepamThe risk or severity of adverse effects can be increased when Zotepine is combined with Zolazepam.Vet Approved
ZolmitriptanThe risk or severity of adverse effects can be increased when Zolmitriptan is combined with Zotepine.Approved, Investigational
ZolpidemZotepine may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.Approved
ZonisamideThe risk or severity of adverse effects can be increased when Zonisamide is combined with Zotepine.Approved, Investigational
ZopicloneThe risk or severity of adverse effects can be increased when Zopiclone is combined with Zotepine.Approved
ZucapsaicinThe metabolism of Zotepine can be decreased when combined with Zucapsaicin.Approved, Investigational
ZuclopenthixolThe risk or severity of adverse effects can be increased when Zuclopenthixol is combined with Zotepine.Approved, Investigational
Food Interactions
Not Available

References

General References
  1. Satoh H, Shimomura K, Mori J: Effect of zotepine on afterdischarge induced by electrical stimulation of amygdaloid nucleus in rats. Jpn J Pharmacol. 1982 Apr;32(2):381-3. [PubMed:6124648]
  2. Bishnoi RJ, Jhanwar VG: Tolerability of zotepine in Indian patients: Preliminary experience. Ind Psychiatry J. 2010 Jul;19(2):130-1. doi: 10.4103/0972-6748.90345. [PubMed:22174537]
  3. Saletu B, Grunberger J, Linzmayer L, Anderer P: Comparative placebo-controlled pharmacodynamic studies with zotepine and clozapine utilizing pharmaco-EEG and psychometry. Pharmacopsychiatry. 1987 Feb;20(1 Spec No):12-27. doi: 10.1055/s-2007-1017125. [PubMed:2883677]
  4. Saletu B, Grunberger J, Anderer P, Chwatal K: [Relation between blood levels and average quantitative EEG and psychometrically assessed pharmacodynamic changes following zotepine]. Fortschr Neurol Psychiatr. 1991 Sep;59 Suppl 1:45-55. doi: 10.1055/s-2007-1000735. [PubMed:1683340]
  5. Noda K, Suzuki A, Okui M, Noguchi H, Nishiura M, Nishiura N: Pharmacokinetics and metabolism of 2-chloro-11-(2-dimethylaminoethoxy)-dibenzo[b,f]thiepine (zotepine) in rat, mouse, dog and man. Arzneimittelforschung. 1979;29(10):1595-600. [PubMed:42414]
  6. Tanaka O, Kondo T, Otani K, Yasui N, Tokinaga N, Kaneko S: Single oral dose kinetics of zotepine and its relationship to prolactin response and side effects. Ther Drug Monit. 1998 Feb;20(1):117-9. [PubMed:9485566]
  7. Wright P. and O'Neill M. (2012). Core psychiatry (3rd ed.). Elsevier.
  8. Macdonald G. and Bartolome J.M. (2010). Progress in Medicinal Chemistry. Lawton and Witty.
  9. FDA Submission [Link]
  10. FDA antipsychotics [Link]
  11. EMA reports [Link]
  12. NIMH [Link]
  13. Zotepine monograph [Link]
External Links
KEGG Drug
D01321
PubChem Compound
5736
PubChem Substance
310265131
ChemSpider
5534
BindingDB
35255
ChEBI
32316
ChEMBL
CHEMBL285802
Wikipedia
Zotepine
ATC Codes
N05AX11 — Zotepine
MSDS
Download (52.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4TerminatedTreatmentSchizophrenic Disorders1
Not AvailableCompletedNot AvailableBipolar Disorder (BD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)90ºC'MSDS'
boiling point (°C)478.4ºC'MSDS'
water solubilityPoorly soluble Patent US6239165
logP4.25'MSDS'
Predicted Properties
PropertyValueSource
Water Solubility0.000777 mg/mLALOGPS
logP4.74ALOGPS
logP4.51ChemAxon
logS-5.6ALOGPS
pKa (Strongest Basic)8.92ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area12.47 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity97.61 m3·mol-1ChemAxon
Polarizability36.21 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as dibenzothiepins. These are compounds containing a dibenzothiepin moiety, which consists of two benzene connected by a thiepine ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzothiepins
Sub Class
Dibenzothiepins
Direct Parent
Dibenzothiepins
Alternative Parents
Diarylthioethers / Benzenoids / Aryl chlorides / Trialkylamines / Organopnictogen compounds / Organooxygen compounds / Organochlorides / Hydrocarbon derivatives
Substituents
Dibenzothiepin / Diarylthioether / Aryl thioether / Aryl chloride / Aryl halide / Benzenoid / Tertiary amine / Tertiary aliphatic amine / Thioether / Organic oxygen compound
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
tertiary amino compound, dibenzothiepine (CHEBI:32316)

Targets

Kind
Protein group
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.

Components:
References
  1. Macdonald G. and Bartolome J.M. (2010). Progress in Medicinal Chemistry. Lawton and Witty.
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Potassium channel regulator activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name
DRD2
Uniprot ID
P14416
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
References
  1. Suzuki H, Gen K, Inoue Y: Comparison of the anti-dopamine D(2) and anti-serotonin 5-HT(2A) activities of chlorpromazine, bromperidol, haloperidol and second-generation antipsychotics parent compounds and metabolites thereof. J Psychopharmacol. 2013 Apr;27(4):396-400. doi: 10.1177/0269881113478281. Epub 2013 Feb 20. [PubMed:23427194]
  2. Macdonald G. and Bartolome J.M. (2010). Progress in Medicinal Chemistry. Lawton and Witty.
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Virus receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
Gene Name
HTR2A
Uniprot ID
P28223
Uniprot Name
5-hydroxytryptamine receptor 2A
Molecular Weight
52602.58 Da
References
  1. Macdonald G. and Bartolome J.M. (2010). Progress in Medicinal Chemistry. Lawton and Witty.
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor ...
Gene Name
HTR6
Uniprot ID
P50406
Uniprot Name
5-hydroxytryptamine receptor 6
Molecular Weight
46953.625 Da
References
  1. Macdonald G. and Bartolome J.M. (2010). Progress in Medicinal Chemistry. Lawton and Witty.
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor ...
Gene Name
HTR7
Uniprot ID
P34969
Uniprot Name
5-hydroxytryptamine receptor 7
Molecular Weight
53554.43 Da
References
  1. Macdonald G. and Bartolome J.M. (2010). Progress in Medicinal Chemistry. Lawton and Witty.
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Norepinephrine:sodium symporter activity
Specific Function
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name
SLC6A2
Uniprot ID
P23975
Uniprot Name
Sodium-dependent noradrenaline transporter
Molecular Weight
69331.42 Da
References
  1. Macdonald G. and Bartolome J.M. (2010). Progress in Medicinal Chemistry. Lawton and Witty.
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Serotonin:sodium symporter activity
Specific Function
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into t...
Gene Name
SLC6A4
Uniprot ID
P31645
Uniprot Name
Sodium-dependent serotonin transporter
Molecular Weight
70324.165 Da
References
  1. Macdonald G. and Bartolome J.M. (2010). Progress in Medicinal Chemistry. Lawton and Witty.

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Zotepine monograph [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Zotepine monograph [Link]

Drug created on October 22, 2015 14:22 / Updated on June 08, 2018 04:40