U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C21H26ClN3OS
Molecular Weight 403.969
Optical Activity UNSPECIFIED
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

Description

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.

CNS Activity

Approval Year

PubMed

PubMed

TitleDatePubMed
Side-effects of phenothiazines.
1967 Apr 1
Phenothiazines in early labour.
1967 Feb 11
Drug-induced extrapyramidal symptoms: their incidence and treatment.
1967 Jan
Oculogyric crises due to phenothiazines.
1967 Jul 22
Specific therapeutic actions of acetophenazine, perphenazine, and benzquinamide in newly admitted schizophrenic patients.
1967 Mar-Apr
Phenothiazines and diabetes in hospitalized women.
1968 Jan
Perphenazine dystonia presenting as recurrent dislocation of the jaw.
1969 Jan
Iatrogenic epilepsy due to antidepressant drugs.
1969 Oct 11
Increased sensitivity to neuroleptics in rats with lesions of the central nervous system.
1972
Idiosyncratic responses to phenothiazines.
1972 Jan 22
Letter: Side-effects of perphenazine.
1975 Jun 21
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
[Acute dystonia in children. 2 cases caused by perphenazine (Trilafon)].
1978 Mar 10
Death attributed to ventricular arrhythmia induced by thioridazine in combination with a single Contac C capsule.
1978 Oct 7
Electrophysiologic studies of perphenazine and protriptyline in a patient with psychotropic drug-induced ventricular fibrillation.
1979 Aug
Seven cases of somnambulism induced by drugs.
1979 Jul
Metoclopramide and dystonic reactions in Sardinians.
1979 Jun 23
Pituitary sensitivity to LHRH in hyperprolactinemia induced by perphenazine and renal pituitary transplants in female rats.
1980 Apr
Plasma levels of perphenazine (Trilafon) related to development of extrapyramidal side effects.
1981
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
Dose-response relationships of perphenazine in the treatment of acute psychoses.
1982
Cerebellar syndrome following neuroleptic induced heat stroke.
1983 Feb
Sigma opiates and certain antipsychotic drugs mutually inhibit (+)-[3H] SKF 10,047 and [3H]haloperidol binding in guinea pig brain membranes.
1984 Sep
Pharmacology in vivo of the phenylindan derivative, Lu 19-005, a new potent inhibitor of dopamine, noradrenaline and 5-hydroxytryptamine uptake in rat brain.
1985 Apr
GABAergic, dopaminergic and cholinergic interactions in perphenazine-induced catatonia in rats.
1985 Dec
Effect of different neuroleptics in tardive dyskinesia and parkinsonism. A video-controlled multicenter study with chlorprothixene, perphenazine, haloperidol and haloperidol + biperiden. Nordic Dyskinesia Study Group.
1986
Tourette-like syndrome following low dose short-term neuroleptic treatment.
1986 May
Neuroleptic malignant syndrome during perphenazine treatment.
1987 Mar
Extrapyramidal symptoms and their relationship to clinical efficacy under perphenazine treatment. A controlled prospective handwriting-test study in 22 acutely ill schizophrenic patients.
1991 Jul
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
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
Clinical characteristics and psychopathological profile of patients with vulvodynia: an observational and descriptive study.
2008
Pharmacologic profiling of human and rat cytochrome P450 1A1 and 1A2 induction and competition.
2008 Dec
[Consumption of inappropriate psychotropic drugs in residential homes for the elderly: comparative study between 2001 and 2006].
2008 Mar-Apr
Acute dystonia induced by the combination of midodrine and perphenazine.
2008 May
A mutual prodrug ester of GABA and perphenazine exhibits antischizophrenic efficacy with diminished extrapyramidal effects.
2008 May 8
BL-1020: a novel antipsychotic drug with GABAergic activity and low catalepsy, is efficacious in a rat model of schizophrenia.
2009 Jan
Identification of selected therapeutic agents as inhibitors of carboxylesterase 1: potential sources of metabolic drug interactions.
2010 Apr 11
Antitubercular pharmacodynamics of phenothiazines.
2013 Apr
Selective inhibition of hepatitis C virus infection by hydroxyzine and benztropine.
2014 Jun
Patents

Sample Use Guides

In Vivo Use Guide
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
In Vitro Use Guide
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
PERPHENAZINE
EP   HSDB   INN   MART.   MI   ORANGE BOOK   USP   USP-RS   VANDF   WHO-DD  
INN  
Official Name English
PERPHENAZINE [EP]
Common Name English
PERPHENAZINE COMPONENT OF ETRAFON-A
Common 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
TRILAFON
Brand Name English
PERPHENAZINE [VANDF]
Common Name English
PERPHENAZINE [MART.]
Common Name English
PERPHENAZINE [USP]
Common Name English
PERPHENAZINE MALEATE [JAN]
Common Name English
PERPHENAZINE [JAN]
Common Name English
PERPHENAZINE [WHO-DD]
Common Name English
NSC-150866
Code English
ETRAFON-A COMPONENT PERPHENAZINE
Common Name English
PERPHENAZINE [INN]
Common Name English
FLUPHENAZINE DIHYDROCHLORIDE IMPURITY E [EP]
Common Name English
PERPHENAZINE [USP-RS]
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 Tue Oct 22 00:45:35 UTC 2019 , Edited by admin on Tue Oct 22 00:45:35 UTC 2019
WHO-VATC QN05AB03
Created by admin on Tue Oct 22 00:45:35 UTC 2019 , Edited by admin on Tue Oct 22 00:45:35 UTC 2019
LIVERTOX 764
Created by admin on Tue Oct 22 00:45:35 UTC 2019 , Edited by admin on Tue Oct 22 00:45:35 UTC 2019
NCI_THESAURUS C29710
Created by admin on Tue Oct 22 00:45:35 UTC 2019 , Edited by admin on Tue Oct 22 00:45:35 UTC 2019
NDF-RT N0000007544
Created by admin on Tue Oct 22 00:45:35 UTC 2019 , Edited by admin on Tue Oct 22 00:45:35 UTC 2019
NDF-RT N0000007544
Created by admin on Tue Oct 22 00:45:35 UTC 2019 , Edited by admin on Tue Oct 22 00:45:35 UTC 2019
NDF-RT N0000007544
Created by admin on Tue Oct 22 00:45:35 UTC 2019 , Edited by admin on Tue Oct 22 00:45:35 UTC 2019
WHO-ATC N05AB03
Created by admin on Tue Oct 22 00:45:35 UTC 2019 , Edited by admin on Tue Oct 22 00:45:35 UTC 2019
Code System Code Type Description
RXCUI
8076
Created by admin on Tue Oct 22 00:45:35 UTC 2019 , Edited by admin on Tue Oct 22 00:45:35 UTC 2019
PRIMARY RxNorm
INN
637
Created by admin on Tue Oct 22 00:45:35 UTC 2019 , Edited by admin on Tue Oct 22 00:45:35 UTC 2019
PRIMARY
EVMPD
SUB09736MIG
Created by admin on Tue Oct 22 00:45:35 UTC 2019 , Edited by admin on Tue Oct 22 00:45:35 UTC 2019
PRIMARY
ChEMBL
CHEMBL567
Created by admin on Tue Oct 22 00:45:35 UTC 2019 , Edited by admin on Tue Oct 22 00:45:35 UTC 2019
PRIMARY
EPA CompTox
58-39-9
Created by admin on Tue Oct 22 00:45:35 UTC 2019 , Edited by admin on Tue Oct 22 00:45:35 UTC 2019
PRIMARY
DRUG BANK
DB00850
Created by admin on Tue Oct 22 00:45:35 UTC 2019 , Edited by admin on Tue Oct 22 00:45:35 UTC 2019
PRIMARY
MESH
D010546
Created by admin on Tue Oct 22 00:45:35 UTC 2019 , Edited by admin on Tue Oct 22 00:45:35 UTC 2019
PRIMARY
WIKIPEDIA
PERPHENAZINE
Created by admin on Tue Oct 22 00:45:35 UTC 2019 , Edited by admin on Tue Oct 22 00:45:35 UTC 2019
PRIMARY
NCI_THESAURUS
C29355
Created by admin on Tue Oct 22 00:45:35 UTC 2019 , Edited by admin on Tue Oct 22 00:45:35 UTC 2019
PRIMARY
PUBCHEM
4748
Created by admin on Tue Oct 22 00:45:35 UTC 2019 , Edited by admin on Tue Oct 22 00:45:35 UTC 2019
PRIMARY
CAS
58-39-9
Created by admin on Tue Oct 22 00:45:35 UTC 2019 , Edited by admin on Tue Oct 22 00:45:35 UTC 2019
PRIMARY
ECHA (EC/EINECS)
200-381-5
Created by admin on Tue Oct 22 00:45:35 UTC 2019 , Edited by admin on Tue Oct 22 00:45:35 UTC 2019
PRIMARY
MERCK INDEX
M8567
Created by admin on Tue Oct 22 00:45:35 UTC 2019 , Edited by admin on Tue Oct 22 00:45:35 UTC 2019
PRIMARY Merck Index
LactMed
58-39-9
Created by admin on Tue Oct 22 00:45:35 UTC 2019 , Edited by admin on Tue Oct 22 00:45:35 UTC 2019
PRIMARY
HSDB
58-39-9
Created by admin on Tue Oct 22 00:45:35 UTC 2019 , Edited by admin on Tue Oct 22 00:45:35 UTC 2019
PRIMARY
IUPHAR
209
Created by admin on Tue Oct 22 00:45:35 UTC 2019 , Edited by admin on Tue Oct 22 00:45:35 UTC 2019
PRIMARY