U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS
This repository is under review for potential modification in compliance with Administration directives.

Details

Stereochemistry ACHIRAL
Molecular Formula C21H26ClN3OS
Molecular Weight 403.969
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PERPHENAZINE

SMILES

OCCN1CCN(CCCN2C3=CC=CC=C3SC4=CC=C(Cl)C=C24)CC1

InChI

InChIKey=RGCVKNLCSQQDEP-UHFFFAOYSA-N
InChI=1S/C21H26ClN3OS/c22-17-6-7-21-19(16-17)25(18-4-1-2-5-20(18)27-21)9-3-8-23-10-12-24(13-11-23)14-15-26/h1-2,4-7,16,26H,3,8-15H2

HIDE SMILES / InChI
Perphenazine is a relatively high potency phenothiazine that blocks dopamine 2 receptors predominantly, but also may possess antagonist actions at histamine 1 and cholinergic M1 and alpha 1 adrenergic receptors in the vomiting center leading to reduced nausea and vomiting. The drug was approved by FDA for the treatment of schizophrenia and control of severe nausea and vomiting (either alone or in combination with amitriptyline hydrochloride). Perphenazine is extensively hepatic to metabolites via sulfoxidation, hydroxylation, dealkylation, and glucuronidation; primarily metabolized by CYP2D6 to N-dealkylated perphenazine, perphenazine sulfoxide, and 7-hydroxyperphenazine (active metabolite with 70% of the activity of perphenazine) and excreted in the urine and feces.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P14416
Gene ID: 1813.0
Gene Symbol: DRD2
Target Organism: Homo sapiens (Human)
0.16 nM [Ki]
Target ID: P35367
Gene ID: 3269.0
Gene Symbol: HRH1
Target Organism: Homo sapiens (Human)
8.0 nM [Kd]
Target ID: P11229
Gene ID: 1128.0
Gene Symbol: CHRM1
Target Organism: Homo sapiens (Human)
1.5 µM [Kd]
10.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
PERPHENAZINE

Approved Use

Perphenazine is indicated for use in the treatment of schizophrenia and for the control of severe nausea and vomiting in adults.

Launch Date

1988
Preventing
PERPHENAZINE

Approved Use

Perphenazine is indicated for use in the treatment of schizophrenia and for the control of severe nausea and vomiting in adults.

Launch Date

1988
Primary
PERPHENAZINE

Approved Use

Perphenazine is indicated for use in the treatment of schizophrenia and for the control of severe nausea and vomiting in adults.

Launch Date

1988
Primary
PERPHENAZINE AND AMITRIPTYLINE HYDROCHLORIDE

Approved Use

Perphenazine and amitriptyline hydrochloride tablets are recommended for treatment of (1) patients with moderate to severe anxiety and/or agitation and depressed mood, (2) patients with depression in whom anxiety and/or agitation are severe, and (3) patients with depression and anxiety in association with chronic physical disease. In many of these patients, anxiety masks the depressive state so that, although therapy with a tranquilizer appears to be indicated, the administration of a tranquilizer alone will not be adequate.

Launch Date

1988
Primary
PERPHENAZINE AND AMITRIPTYLINE HYDROCHLORIDE

Approved Use

Perphenazine and amitriptyline hydrochloride tablets are recommended for treatment of (1) patients with moderate to severe anxiety and/or agitation and depressed mood, (2) patients with depression in whom anxiety and/or agitation are severe, and (3) patients with depression and anxiety in association with chronic physical disease. In many of these patients, anxiety masks the depressive state so that, although therapy with a tranquilizer appears to be indicated, the administration of a tranquilizer alone will not be adequate.

Launch Date

1988
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0.546 ng/mL
16 mg single, oral
dose: 16 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PERPHENAZINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
984 pg/mL
4 mg 3 times / day steady-state, oral
dose: 4 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
PERPHENAZINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
509 pg/mL
4 mg 3 times / day steady-state, oral
dose: 4 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
7-HYDROXYPERPHENAZINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
6.673 ng × h/mL
16 mg single, oral
dose: 16 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PERPHENAZINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
9.12 h
16 mg single, oral
dose: 16 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PERPHENAZINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
12 h
4 mg 3 times / day steady-state, oral
dose: 4 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
PERPHENAZINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
18.8 h
4 mg 3 times / day steady-state, oral
dose: 4 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
7-HYDROXYPERPHENAZINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
9%
unknown, unknown
PERPHENAZINE unknown
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
0.93 g single, oral
Overdose
Dose: 0.93 g
Route: oral
Route: single
Dose: 0.93 g
Sources:
unhealthy, 42
Health Status: unhealthy
Age Group: 42
Sex: M
Sources:
Disc. AE: QT interval prolonged, Hypothermia...
AEs leading to
discontinuation/dose reduction:
QT interval prolonged
Hypothermia
Loss of consciousness
PR interval prolonged
QRS prolonged
Sources:
200 mg single, oral
Overdose
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources:
unhealthy, 48
Health Status: unhealthy
Age Group: 48
Sex: F
Sources:
Disc. AE: Coma, Hypothermia...
AEs leading to
discontinuation/dose reduction:
Coma
Hypothermia
Tachycardia
Miosis
Sources:
30 mg 1 times / day multiple, intramuscular
Recommended
Dose: 30 mg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 30 mg, 1 times / day
Sources:
unhealthy
Disc. AE: Tardive dyskinesia...
AEs leading to
discontinuation/dose reduction:
Tardive dyskinesia
Sources:
30 mg 1 times / day multiple, intramuscular
Recommended
Dose: 30 mg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 30 mg, 1 times / day
Sources:
unhealthy
Disc. AE: Neuroleptic malignant syndrome...
AEs leading to
discontinuation/dose reduction:
Neuroleptic malignant syndrome
Sources:
64 mg 1 times / day multiple, oral
Recommended
Dose: 64 mg, 1 times / day
Route: oral
Route: multiple
Dose: 64 mg, 1 times / day
Sources:
unhealthy
Disc. AE: Tardive dyskinesia...
AEs leading to
discontinuation/dose reduction:
Tardive dyskinesia
Sources:
64 mg 1 times / day multiple, oral
Recommended
Dose: 64 mg, 1 times / day
Route: oral
Route: multiple
Dose: 64 mg, 1 times / day
Sources:
unhealthy
Disc. AE: Neuroleptic malignant syndrome...
AEs leading to
discontinuation/dose reduction:
Neuroleptic malignant syndrome
Sources:
20 mg single, intramuscular
Studied dose
Dose: 20 mg
Route: intramuscular
Route: single
Dose: 20 mg
Sources:
unhealthy
Health Status: unhealthy
Sources:
Disc. AE: Neuroleptic malignant syndrome...
AEs leading to
discontinuation/dose reduction:
Neuroleptic malignant syndrome
Sources:
AEs

AEs

AESignificanceDosePopulation
Hypothermia Disc. AE
0.93 g single, oral
Overdose
Dose: 0.93 g
Route: oral
Route: single
Dose: 0.93 g
Sources:
unhealthy, 42
Health Status: unhealthy
Age Group: 42
Sex: M
Sources:
Loss of consciousness Disc. AE
0.93 g single, oral
Overdose
Dose: 0.93 g
Route: oral
Route: single
Dose: 0.93 g
Sources:
unhealthy, 42
Health Status: unhealthy
Age Group: 42
Sex: M
Sources:
PR interval prolonged Disc. AE
0.93 g single, oral
Overdose
Dose: 0.93 g
Route: oral
Route: single
Dose: 0.93 g
Sources:
unhealthy, 42
Health Status: unhealthy
Age Group: 42
Sex: M
Sources:
QRS prolonged Disc. AE
0.93 g single, oral
Overdose
Dose: 0.93 g
Route: oral
Route: single
Dose: 0.93 g
Sources:
unhealthy, 42
Health Status: unhealthy
Age Group: 42
Sex: M
Sources:
QT interval prolonged Disc. AE
0.93 g single, oral
Overdose
Dose: 0.93 g
Route: oral
Route: single
Dose: 0.93 g
Sources:
unhealthy, 42
Health Status: unhealthy
Age Group: 42
Sex: M
Sources:
Coma Disc. AE
200 mg single, oral
Overdose
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources:
unhealthy, 48
Health Status: unhealthy
Age Group: 48
Sex: F
Sources:
Hypothermia Disc. AE
200 mg single, oral
Overdose
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources:
unhealthy, 48
Health Status: unhealthy
Age Group: 48
Sex: F
Sources:
Miosis Disc. AE
200 mg single, oral
Overdose
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources:
unhealthy, 48
Health Status: unhealthy
Age Group: 48
Sex: F
Sources:
Tachycardia Disc. AE
200 mg single, oral
Overdose
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources:
unhealthy, 48
Health Status: unhealthy
Age Group: 48
Sex: F
Sources:
Tardive dyskinesia Disc. AE
30 mg 1 times / day multiple, intramuscular
Recommended
Dose: 30 mg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 30 mg, 1 times / day
Sources:
unhealthy
Neuroleptic malignant syndrome Disc. AE
30 mg 1 times / day multiple, intramuscular
Recommended
Dose: 30 mg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 30 mg, 1 times / day
Sources:
unhealthy
Tardive dyskinesia Disc. AE
64 mg 1 times / day multiple, oral
Recommended
Dose: 64 mg, 1 times / day
Route: oral
Route: multiple
Dose: 64 mg, 1 times / day
Sources:
unhealthy
Neuroleptic malignant syndrome Disc. AE
64 mg 1 times / day multiple, oral
Recommended
Dose: 64 mg, 1 times / day
Route: oral
Route: multiple
Dose: 64 mg, 1 times / day
Sources:
unhealthy
Neuroleptic malignant syndrome Disc. AE
20 mg single, intramuscular
Studied dose
Dose: 20 mg
Route: intramuscular
Route: single
Dose: 20 mg
Sources:
unhealthy
Health Status: unhealthy
Sources:
Overview

Overview

Drug as perpetrator​Drug as victimTox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
Dystonic reaction to perphenazine.
1969 Aug 9
[Psychometric effects of perphenacine below the "neuroleptic threshold" (author's transl)].
1975 Dec
Drug-induced dystonia.
1975 May
Tetany, tetanus or drug reaction? A case report.
1976 Jul
Asymptomatic idiopathic syndrome of prolonged Q-T interval in a 45-year-old woman. Ventricular tachyarrhythmias precipitated by hypokalemia and therapy with amitriptyline and prephenazine.
1977 Feb
Drug-induced anaphylaxis, convulsions, deafness, and extrapyramidal symptoms.
1977 Mar 12
Death attributed to ventricular arrhythmia induced by thioridazine in combination with a single Contac C capsule.
1978 Oct 7
Metoclopramide and dystonic reactions in Sardinians.
1979 Jun 23
Toxic psychosis with cimetidine.
1979 May
Actions of clonidine on convulsions and behaviour.
1981 Jul
Prolactin and the small intestine. Effect of hyperprolactinaemia on mucosal structure in the rat.
1981 Jul
Tricyclic antidepressants and alcoholic blackouts.
1981 Jun
GABAergic, dopaminergic and cholinergic interactions in perphenazine-induced catatonia in rats.
1985 Dec
D1/D2 dopamine and N-methyl-D-aspartate (NMDA) receptor participation in experimental catalepsy in rats.
1992
Risperidone versus perphenazine in the treatment of chronic schizophrenic patients with acute exacerbations.
1993 Dec
Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors.
1994 Mar
The efficacy of prophylactic ondansetron, droperidol, perphenazine, and metoclopramide in the prevention of nausea and vomiting after major gynecologic surgery.
1995 Jul
BMY-14802 reversed the sigma receptor agonist-induced neck dystonia in rats.
1996
Association of plasma homovanillic acid with behavioral symptoms in patients diagnosed with dementia: a preliminary report.
1997 Dec 1
Induction of mania by risperidone resistant to mood stabilizers.
1997 Feb
Olanzapine use in women with antipsychotic-induced hyperprolactinemia.
1998 Oct
Acquired aplastic anemia secondary to perphenazine.
1999 Autumn
Perphenazine-induced hiccups.
1999 Mar
[Diabetes mellitus after treatment with clozapine].
2000 Feb 26
Antipsychotic-induced extrapyramidal syndromes. Risperidone compared with low- and high-potency conventional antipsychotic drugs.
2001 Jul
Role of adenosine in drug-induced catatonia in mice.
2002 Aug
Drug-induced toxic myocarditis.
2003
Quercetin potentiates L-Dopa reversal of drug-induced catalepsy in rats: possible COMT/MAO inhibition.
2003 Jun
H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs.
2003 Mar
Survey on schizophrenia treatment in Mexico: perception and antipsychotic prescription patterns.
2004 Apr 27
PASS assisted search and evaluation of some azetidin-2-ones as C.N.S. active agents.
2005 Aug 3
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
[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 Jun
Nerve growth factor mRNA expression in the regenerating antler tip of red deer (Cervus elaphus).
2007 Jan 10
[Consumption of inappropriate psychotropic drugs in residential homes for the elderly: comparative study between 2001 and 2006].
2008 Mar-Apr
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.
2011 Jul 14
Selective inhibition of hepatitis C virus infection by hydroxyzine and benztropine.
2014 Jun
Patents

Sample Use Guides

Moderately disturbed nonhospitalized patients with schizophrenia: 4 to 8 mg t.i.d. initially; reduce as soon as possible to minimum effective dosage. Hospitalized patients with schizophrenia: 8 to 16 mg b.i.d. to q.i.d.; avoid dosages in excess of 64 mg daily. Severe nausea and vomiting in adults: 8 to 16 mg daily in divided doses; 24 mg occasionally may be necessary; early dosage reduction is desirable.
Route of Administration: Oral
Perphenazine (10-100 microM) was administered, either alone or combined with dopamine, to primary mouse neuronal or intact brain culture and to a human neuroblastoma (NB) cell line (SK-N-SH). Cell viability (measured by neutral red and alamar blue), DNA fragmentation (flow cytometry-NB) were determined. Neuroblastoma: perphenazine decreased viability by 87%.
Name Type Language
TRILAFON
Preferred Name English
PERPHENAZINE
EP   HSDB   INN   MART.   MI   ORANGE BOOK   USP   USP-RS   VANDF   WHO-DD  
INN  
Official Name English
PIPERAZINEETHANOL, 4-(3-(2-CHLORO-10H-PHENOTHIAZIN-10-YL)PROPYL)-
Systematic Name English
PERPHENAZINE [HSDB]
Common Name English
4-[3-(2-Chlorophenothiazin-10-yl)propyl]-1-piperazineethanol
Systematic Name English
PERPHENAZINE [VANDF]
Common Name English
PERPHENAZINE [USP MONOGRAPH]
Common Name English
PERPHENAZINE [MART.]
Common Name English
Perphenazine [WHO-DD]
Common Name English
PERPHENAZINE MALEATE [JAN]
Common Name English
PERPHENAZINE [JAN]
Common Name English
NSC-150866
Code English
PERPHENAZINE [EP MONOGRAPH]
Common Name English
ETRAFON-A COMPONENT PERPHENAZINE
Common Name English
perphenazine [INN]
Common Name English
PERPHENAZINE [USP-RS]
Common Name English
FLUPHENAZINE DIHYDROCHLORIDE IMPURITY E [EP IMPURITY]
Common Name English
PERPHENAZINE [ORANGE BOOK]
Common Name English
PERPHENAZINE [MI]
Common Name English
Classification Tree Code System Code
NDF-RT N0000175746
Created by admin on Mon Mar 31 18:28:34 GMT 2025 , Edited by admin on Mon Mar 31 18:28:34 GMT 2025
WHO-VATC QN05AB03
Created by admin on Mon Mar 31 18:28:34 GMT 2025 , Edited by admin on Mon Mar 31 18:28:34 GMT 2025
LIVERTOX NBK548366
Created by admin on Mon Mar 31 18:28:34 GMT 2025 , Edited by admin on Mon Mar 31 18:28:34 GMT 2025
NCI_THESAURUS C29710
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NDF-RT N0000007544
Created by admin on Mon Mar 31 18:28:34 GMT 2025 , Edited by admin on Mon Mar 31 18:28:34 GMT 2025
NDF-RT N0000007544
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NDF-RT N0000007544
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WHO-ATC N05AB03
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Code System Code Type Description
RXCUI
8076
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PRIMARY RxNorm
INN
637
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PRIMARY
EVMPD
SUB09736MIG
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PRIMARY
ChEMBL
CHEMBL567
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PRIMARY
EPA CompTox
DTXSID1023441
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PRIMARY
DRUG BANK
DB00850
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PRIMARY
FDA UNII
FTA7XXY4EZ
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PRIMARY
MESH
D010546
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PRIMARY
DAILYMED
FTA7XXY4EZ
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PRIMARY
WIKIPEDIA
PERPHENAZINE
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PRIMARY
NCI_THESAURUS
C29355
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PRIMARY
CHEBI
8028
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PRIMARY
DRUG CENTRAL
2113
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PRIMARY
NSC
150866
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PRIMARY
RS_ITEM_NUM
1511000
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PRIMARY
PUBCHEM
4748
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PRIMARY
SMS_ID
100000092394
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PRIMARY
CAS
58-39-9
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PRIMARY
ECHA (EC/EINECS)
200-381-5
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PRIMARY
MERCK INDEX
m8567
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PRIMARY Merck Index
HSDB
3379
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PRIMARY
LACTMED
Perphenazine
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PRIMARY
IUPHAR
209
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PRIMARY