PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
perphenazine

2D structure

Overview

Generic Names: Chlorperphenazine; Etaperazin; Etaperazine; Ethaperazine; PZC; Perfenazina; Perfenazine; Perphenazin
Trade Names: Apo-Perphenazine; Decentan; Emesinal; Etrafon-A; Etrafon-Forte; F-Mon; Fentazin; Perphenan; Thilatazin; Trifaron; Trilafon; Trilifan; Triphenot
Brand Mixtures: Apo Peram Tab 2-25 (Amitriptyline Hydrochloride + Perphenazine); Apo Peram Tab 3-15 (Amitriptyline Hydrochloride + Perphenazine); Elavil Plus Tab (Amitriptyline Hydrochloride + Perphenazine); Etrafon 2 10 (Amitriptyline Hydrochloride + Perphenazine); Etrafon D Tab (Amitriptyline Hydrochloride + Perphenazine); Etrafon F Tab (Amitriptyline Hydrochloride + Perphenazine); Etrafon a Tab (Amitriptyline Hydrochloride + Perphenazine); Pms-Levazine 2/25 Tab (Amitriptyline Hydrochloride + Perphenazine); Pms-Levazine 3/15 Tab (Amitriptyline Hydrochloride + Perphenazine); Pms-Levazine 4/25 Tab (Amitriptyline Hydrochloride + Perphenazine); Proavil Tab (Amitriptyline Hydrochloride + Perphenazine); Triavil Tab (Amitriptyline Hydrochloride + Perphenazine)
PharmGKB Accession Id: PA450882

Description

An antipsychotic phenothiazine derivative with actions and uses similar to those of chlorpromazine. PubChem (source: Drug Bank)

Indication

For use in the management of the manifestations of psychotic disorders and for the control of severe nausea and vomiting in adults. (source: Drug Bank)

ATC Therapeutic Category

  • N05AB:Phenothiazines with piperazine structure

Pharmacology, Interactions, and Contraindications

Mechanism Of Action

Binds to the dopamine D1 and dopamine D2 receptors and inhibits their activity. The mechanism of the anti-emetic effect is due predominantly to blockage of the dopamine D2 neurotransmitter receptors in the chemoreceptor trigger zone and vomiting centre. Perphenazine also binds the alpha andrenergic receptor. This receptor's action is mediated by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. (source: Drug Bank)

Pharmacology

Perphenazine is a piperazinyl phenothiazine, acts on the central nervous system, and has a greater behavioral potency than other phenothiazine derivatives whose side chains do not contain a piperazine moiety. It is a member of a class of drugs called phenothiazines, which are dopamine D1/D2 receptor antagonists. Perphenazine is 10 to 15 times as potent as chlorpromazine; that means perphenazine is a highly potent antipsychotic. In equivalent doses it has approximately the same frequency and severity of early and late extrapypramidal side-effects compared to Haloperidol. (source: Drug Bank)

Food Interactions

Avoid alcohol.
Do not take calcium, aluminum, magnesium or Iron supplements within 2 hours of taking this medication.
Take with food. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic. (source: Drug Bank)

Absorption

Absolute bioavailability is 40% following oral administration. (source: Drug Bank)

Toxicity

Symptoms of overdose include stupor or coma, and children may have convulsive seizures. Signs of arousal may not occur for 48 hours. Oral LD<sub>50</sub>=318 mg/kg (rat); IPR LD<sub>50</sub>=64 mg/kg (mouse) (source: Drug Bank)

Isomeric SMILES Code:

c1ccc2c(c1)N(c3cc(ccc3S2)Cl)CCCN4CCN(CC4)CCO (source: Drug Bank)

Curated Annotations (Curated Annotation)

  1. rs951439 at chr1:161300315 in RGS4
    This variant is associated with differential antipsychotic treatment response in individuals of african descent. Patients with african descent and rs951439 genotype CC responded better to perphenazine treatment compared with ziprasidone or quetiapine treatments. Patient with European descent and rs951439 TT genotype responded better to risperidone than those with CC genotype. However, no association was find between this variant and incidence or age at onset in schizophrenia as well as treatment responses in Finnish patients.
    Related Drugs:
    perphenazine, quetiapine, risperidone, ziprasidone
    Related Diseases:
    Schizophrenia
    Evidence:
    PMID:16604300
    PMID:17588543
    PMID:18204343
  2. rs2661319 at chr1:161306401 in RGS4
    This variant is associated with differential antipsychotic treatment response in individuals of african descent and chinese descent.
    Related Drugs:
    perphenazine, quetiapine, risperidone, ziprasidone
    Related Diseases:
    Schizophrenia
    Evidence:
    PMID:17588543
    PMID:18204343
  3. rs2842030 at chr1:161307119 in RGS4
    This variant is associated with differential antipsychotic treatment response in individuals of african descent. Patient with rs2842030 TT genotype responded better to perphenazine treatment than by quatiapine, risperidone or ziprasidone. Patient with European descent and rs2842030 GG genotype responded better to risperidone than those with TT genotype.No association was found between this variant and increased susceptibility to the etiology of schizophrenia in Han Chinese.
    Related Drugs:
    perphenazine, quetiapine, risperidone, ziprasidone
    Related Diseases:
    Schizophrenia
    Evidence:
    PMID:16904822
    PMID:17588543
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2D6
  • CO
  • PD
  • PK
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Has annotations
DRD2
  •   
  • PD
  • PK
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
RGS4
  •   
  •   
  •   
  •   
  •   
Variants

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

Gene Description
ADRA1A Uncurated Annotation (source: Drug Bank)
CALM1 Uncurated Annotation (source: Drug Bank)
CALM3 Uncurated Annotation (source: Drug Bank)
CYP2D6 Uncurated Annotation (source: Drug Bank)
DRD1 Uncurated Annotation (source: Drug Bank)
DRD2 Uncurated Annotation (source: Drug Bank)

The following drugs are in curated knowledge about this drug.

  Drug Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
paroxetine
  •   
  •   
  •   
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
tamoxifen
  •   
  •   
  •   
  •   
  •   
Publications

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

Drug Description
amphetamine Uncurated Annotation Decreased anorexic effect, may increase psychotic symptoms (source: Drug Bank)
atomoxetine Uncurated Annotation The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine (source: Drug Bank)
benzphetamine Uncurated Annotation Decreased anorexic effect, may increase psychotic symptoms (source: Drug Bank)
bromocriptine Uncurated Annotation The phenothiazine decreases the effect of bromocriptine (source: Drug Bank)
cisapride Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
dexfenfluramine Uncurated Annotation Decreased anorexic effect, may increase psychotic symptoms (source: Drug Bank)
dextroamphetamine Uncurated Annotation Decreased anorexic effect, may increase psychotic symptoms (source: Drug Bank)
diethylpropion Uncurated Annotation Decreased anorexic effect, may increase psychotic symptoms (source: Drug Bank)
donepezil Uncurated Annotation Possible antagonism of action (source: Drug Bank)
fenfluramine Uncurated Annotation Decreased anorexic effect, may increase psychotic symptoms (source: Drug Bank)
galantamine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
gatifloxacin Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
grepafloxacin Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
guanethidine Uncurated Annotation The agent decreases the effect of guanethidine (source: Drug Bank)
levofloxacin Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
mazindol Uncurated Annotation Decreased anorexic effect, may increase psychotic symptoms (source: Drug Bank)
methamphetamine Uncurated Annotation Decreased anorexic effect, may increase psychotic symptoms (source: Drug Bank)
metrizamide Uncurated Annotation Increased risk of convulsions (source: Drug Bank)
phendimetrazine Uncurated Annotation Decreased anorexic effect, may increase psychotic symptoms (source: Drug Bank)
phenmetrazine Uncurated Annotation Decreased anorexic effect, may increase psychotic symptoms (source: Drug Bank)
phentermine Uncurated Annotation Decreased anorexic effect, may increase psychotic symptoms (source: Drug Bank)
phenylpropanolamine Uncurated Annotation Decreased anorexic effect, may increase psychotic symptoms (source: Drug Bank)
rivastigmine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
sparfloxacin Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
terfenadine Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00850
KEGG Compound ID:
C07427
KEGG Drug ID:
D00503
PubChem Compound ID:
4748
PubChem Substance ID:
148869
IUPHAR Ligand ID:
209

Common Searches

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.

PharmGKB integrates drug information from different sources: DrugBank, Open Eye Scientific Software.
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