PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
chlorpromazine

2D structure

Overview

Trade Names: Chloropromazine; Chlorpromanyl-20; Chlorpromanyl-40; Chlorpromazine Hydrochloride Intensol; Largactil Liquid; Largactil Oral Drops; Novo-Chlorpromazine; Thorazine Spansule
PharmGKB Accession Id: PA448964

Description

The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. PubChem (source: Drug Bank)

Indication

For the treatment of schizophrenia, control nausea and vomiting, For relief of restlessness and apprehension before surgery, adjunct in the treatment of tetanus, control the manifestations of the manic type of manic-depressive illness. (source: Drug Bank)

ATC Therapeutic Category

  • N05AA:Phenothiazines with aliphatic side-chain

Pharmacology, Interactions, and Contraindications

Mechanism Of Action

Chlorpromazine acts as an antagonist (blocking agent) on different postsysnaptic receptors -on dopaminergic-receptors (subtypes D1, D2, D3 and D4 - different antipsychotic properties on productive and unproductive symptoms), on serotonergic-receptors (5-HT1 and 5-HT2, with anxiolytic, antidepressive and antiaggressive properties as well as an attenuation of extrapypramidal side-effects, but also leading to weight gain, fall in blood pressure, sedation and ejaculation difficulties), on histaminergic-receptors (H1-receptors, sedation, antiemesis, vertigo, fall in blood pressure and weight gain), alpha1/alpha2-receptors (antisympathomimetic properties, lowering of blood pressure, reflex tachycardia, vertigo, sedation, hypersalivation and incontinence as well as sexual dysfunction, but may also attenuate pseudoparkinsonism - controversial) and finally on muscarinic (cholinergic) M1/M2-receptors (causing anticholinergic symptoms like dry mouth, blurred vision, obstipation, difficulty/inability to urinate, sinus tachycardia, ECG-changes and loss of memory, but the anticholinergic action may attenuate extrapyramidal side-effects).
Additionally, Chlorpromazine is a weak presynaptic inhibitor of Dopamine reuptake, which may lead to (mild) antidepressive and antiparkinsonian effects. This action could also account for psychomotor agitation and amplification of psychosis (very rarely noted in clinical use). (source: Drug Bank)

Pharmacology

Chlorpromazine is a psychotropic agent indicated for the treatment of schizophrenia. It also exerts sedative and antiemetic activity. Chlorpromazine has actions at all levels of the central nervous system-primarily at subcortical levels-as well as on multiple organ systems. Chlorpromazine has strong antiadrenergic and weaker peripheral anticholinergic activity; ganglionic blocking action is relatively slight. It also possesses slight antihistaminic and antiserotonin activity. (source: Drug Bank)

Food Interactions

Avoid alcohol.
Take with food to reduce irritation. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

Protein Binding

40% (source: Drug Bank)

Toxicity

Agitation, coma, convulsions, difficulty breathing, difficulty swallowing, dry mouth, extreme sleepiness, fever, intestinal blockage, irregular heart rate, low blood pressure, restlessness (source: Drug Bank)

Isomeric SMILES Code:

CN(C)CCCN1c2ccccc2Sc3c1cc(cc3)Cl (source: Drug Bank)

Curated Annotations (Curated Annotation)

  1. rs1800497 at chr11:112776038 in ANKK1
    Phenotype: A meta-analysis, including eight individual studies, was not able to detect an association between clinical response to antipsychotics and the Taq1A variant. Study size: meta-analysis included 8 individual studies, 748 patients total.
    Variant Name:
    TaqIA (C/T)
    Related Drugs:
    aripiprazole, Bromperidol, chlorpromazine, clozapine, haloperidol, nemonapride, risperidone
    Related Diseases:
    Schizophrenia
    Evidence:
    PMID:20194480
  2. rs1799732 at chr11:112851462 in DRD2
    Phenotype: The −141C Ins/Del polymorphism was found to be significantly related to the therapeutic effect of chlorpromazine in schizophrenia patients (P = 0.01). Patients with no Del allele showed greater improvement than those with Del allele on the overall Brief Psychiatry Rating Scale (P=0.03). For the TaqI A SNP (rs1800497) no significant difference in genotype was observed between drug responder and non-responder groups (P = 0.99). Study size: 135 inpatients. Study population: Chinese.
    Variant Name:
    DRD2: -141C Ins/Del
    Related Drugs:
    chlorpromazine
    Related Diseases:
    Schizophrenia
    Evidence:
    PMID:15694263
  3. rs1799732 at chr11:112851462 in DRD2
    Phenotype: Results of this meta-analysis showed that the group of Del allele carrier was significantly associated with poorer antipsychotic drug response relative to the Ins/Ins genotype. Study size: meta-analysis included six individual studies, 687 patients total.
    Variant Name:
    DRD2: -141C Ins/Del
    Related Drugs:
    aripiprazole, chlorpromazine, clozapine, olanzapine, risperidone
    Related Diseases:
    Schizophrenia
    Evidence:
    PMID:20194480
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
ABCB1
  •   
  •   
  • PK
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
ANKK1
  •   
  •   
  •   
  •   
  •   
Variants
No phenotype data No genotype data Literature annotations available Not annotated
BDNF
  • CO
  •   
  •   
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2D6
  •   
  •   
  • PK
  •   
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
CYP2E1
  •   
  •   
  • PK
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Has annotations
DRD2
  •   
  •   
  •   
  •   
  •   
Variants
Phenotype data available Genotype Data Available Literature annotations available Has annotations
NR1I2
  •   
  •   
  •   
  • FA
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
UGT1A4
  •   
  •   
  • PK
  •   
  •   
Publications

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

Drug Targets

Gene Description
HTR2A Uncurated Annotation (source: Drug Bank)
ALB Uncurated Annotation (source: Drug Bank)
DRD2 Uncurated Annotation (source: Drug Bank)

The following drugs are in curated knowledge about this drug.

  Drug Relationship Evidence
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)
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 increases psychotic symptoms (source: Drug Bank)
dextroamphetamine Uncurated Annotation Decreased anorexic effect, may increases 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)
meperidine Uncurated Annotation Increased sedation and hypotension (source: Drug Bank)
mesoridazine Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
methamphetamine Uncurated Annotation Decreased anorexic effect, may increases psychotic symptoms (source: Drug Bank)
metrizamide Uncurated Annotation Increased risk of convulsions (source: Drug Bank)
phendimetrazine Uncurated Annotation Decreased anorexic effect, may increases 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)
pindolol Uncurated Annotation Increased effect of both drugs (source: Drug Bank)
propranolol Uncurated Annotation Increased effect of both drugs (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)
thioridazine Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
ziprasidone Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Not annotated
Parkinson Disease
  •   
  • PD
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Schizophrenia
  • CO
  •   
  •   
  •   
  • GN
Publications, Variants

Non-Curated Information

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

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00477
KEGG Compound ID:
C06906
KEGG Drug ID:
D00270
PubChem Compound ID:
2726
PubChem Substance ID:
148556
IUPHAR Ligand ID:
83

Common Searches

Search PubMed
Search Medline Plus
Search PubChem
Search CTD

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.
Add New Alternate Name
Add New ATC Term
Add Cross Reference
Add a metabolite
Add a text annotation
Add a drug target
hint: enter a gene
    Add a drug interaction
    hint: enter a drug
    PharmGKB® is a registered trademark of HHS and is financially supported by NIH/NIGMS. It is managed at Stanford University (GM61374).
    ©2001-2010 PharmGKB.