PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
pimozide

2D structure

Overview

Generic Names: Pimozida [INN-Spanish]; Pimozidum [INN-Latin]
IUPAC Name: 3-[1-[4,4-bis(4-fluorophenyl)butyl]piperidin-4-yl]-1H-benzimidazol-2-one
Trade Names: Halomonth; Neoperidole; Opiran; Orap
PharmGKB Accession Id: PA450965

Description

A diphenylbutylpiperidine that is effective as an antipsychotic agent and as an alternative to haloperidol for the suppression of vocal and motor tics in patients with Tourette syndrome. Although the precise mechanism of action is unknown, blockade of postsynaptic dopamine receptors has been postulated. (From AMA Drug Evaluations Annual, 1994, p403)

Indication

Used for the suppression of motor and phonic tics in patients with Tourette's Disorder who have failed to respond satisfactorily to standard treatment.

ATC Therapeutic Category

  • N05AG:Diphenylbutylpiperidine derivatives

Pharmacology and Interactions

Mechanism Of Action

The ability of pimozide to suppress motor and phonic tics in Tourette's Disorder is thought to be primarily a function of its dopaminergic blocking activity. Pimozide binds to the dopamine D2 receptor in the CNS. It also appears to block voltage-operated calcium channels and acts as an antagonist at opiate receptors (OP2).

Pharmacology

Pimozide is an orally active antipsychotic drug product which shares with other antipsychotics the ability to blockade dopaminergic receptors on neurons in the central nervous system. However, receptor blockade is often accompanied by a series of secondary alterations in central dopamine metabolism and function which may contribute to both pimozide's therapeutic and untoward effects. In addition, pimozide, in common with other antipsychotic drugs, has various effects on other central nervous system receptor systems which are not fully characterized. Pimozide also has less potential for inducing sedation and hypotension as it has more specific dopamine receptor blocking activity than other neuroleptic agents (and is therefore a suitable alternative to haloperidol).

Food Interactions

Grapefruit and grapefruit juice should be avoided throughout treatment. Grapefruit can increase serum levels of this product. Take without regard to meals.

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Notable first-pass metabolism in the liver, primarily by N-dealkylation via the cytochrome P450 isoenzymes CYP3A and CYP1A2 (and possibly CYP2D6). The activity of the two major metabolites has not been determined.

Absorption

Greater than 50% absorption after oral administration. Serum peak appears 6-8 hours post ingestion.

Half Life

29 ± 10 hours (single-dose study of healthy volunteers).

Toxicity

LD50 = 1100 mg/kg (rat, oral), 228 mg/kg (mouse, oral)

Chemical Properties

Chemical Formula:

C28H29F2N3O

SMILES Code:

c1ccc2c(c1)[nH]c(=O)n2C3CCN(CC3)CCCC(c4ccc(cc4)F)c5ccc(cc5)F

(Format: OpenEye Isomeric)

Molecular Weight ( average / monoisotopic )

461.5462 / 461.2279

Curated Information

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
No phenotype data Genotype Data Available Literature annotations available Not annotated
ABCC8
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No phenotype data Genotype Data Available Literature annotations available Not annotated
ABCC9
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No phenotype data Genotype Data Available Literature annotations available Not annotated
ADRA1D
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No phenotype data Genotype Data Available Literature annotations available Not annotated
ADRA2A
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Phenotype data available Genotype Data Available Literature annotations available Has annotations
ADRB1
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Phenotype data available Genotype Data Available Literature annotations available Has annotations
ADRB2
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No phenotype data Genotype Data Available Literature annotations available Not annotated
ANK2
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Pathways
Phenotype data available No genotype data Literature annotations available Not annotated
ATP1A1
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No phenotype data No genotype data Literature annotations available Not annotated
ATP2A1
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No phenotype data No genotype data Literature annotations available Not annotated
ATP2A2
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No phenotype data No genotype data Literature annotations available Not annotated
CACNA1C
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No phenotype data Genotype Data Available Literature annotations available Not annotated
CACNA1D
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No phenotype data No genotype data Literature annotations available Not annotated
CACNA1G
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CACNA1H
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No phenotype data No genotype data No literature annotations Not annotated
CACNB2
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No phenotype data No genotype data Literature annotations available Not annotated
CASQ1
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No phenotype data No genotype data Literature annotations available Not annotated
CASQ2
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No phenotype data Genotype Data Available Literature annotations available Not annotated
CHRM2
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
DSP
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FKBP1B
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GJA1
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GJA5
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No phenotype data No genotype data Literature annotations available Not annotated
GJD3
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No phenotype data No genotype data Literature annotations available Not annotated
HCN2
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No phenotype data No genotype data Literature annotations available Not annotated
HCN4
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Phenotype data available No genotype data Literature annotations available Not annotated
JUP
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Pathways
Phenotype data available Genotype Data Available Literature annotations available Not annotated
KCNA5
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
KCNAB2
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Pathways
No phenotype data Genotype Data Available Literature annotations available Not annotated
KCND3
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Pathways
Phenotype data available Genotype Data Available Literature annotations available Not annotated
KCNE1
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Pathways
No phenotype data Genotype Data Available No literature annotations Not annotated
KCNE1L
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Phenotype data available Genotype Data Available Literature annotations available Not annotated
KCNE2
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No phenotype data Genotype Data Available Literature annotations available Not annotated
KCNE3
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No phenotype data Genotype Data Available Literature annotations available Not annotated
KCNE4
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Pathways
Phenotype data available Genotype Data Available Literature annotations available Has annotations
KCNH2
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Publications, Pathways
No phenotype data No genotype data Literature annotations available Not annotated
KCNIP2
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Pathways
No phenotype data Genotype Data Available Literature annotations available Has annotations
KCNJ11
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
KCNJ2
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No phenotype data No genotype data Literature annotations available Not annotated
KCNJ3
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No phenotype data No genotype data Literature annotations available Not annotated
KCNJ4
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No phenotype data No genotype data Literature annotations available Not annotated
KCNJ5
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No phenotype data No genotype data Literature annotations available Not annotated
KCNJ8
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No phenotype data No genotype data Literature annotations available Not annotated
KCNK1
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No phenotype data No genotype data Literature annotations available Not annotated
KCNK3
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KCNQ1
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No phenotype data No genotype data Literature annotations available Not annotated
LMNA
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PLN
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No phenotype data No genotype data Literature annotations available Not annotated
RYR2
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No phenotype data Genotype Data Available Literature annotations available Not annotated
SCN1B
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No phenotype data Genotype Data Available Literature annotations available Not annotated
SCN2B
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No phenotype data Genotype Data Available Literature annotations available Not annotated
SCN3B
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No phenotype data No genotype data Literature annotations available Not annotated
SCN4B
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Pathways
Phenotype data available Genotype Data Available Literature annotations available Has annotations
SCN5A
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
SLC8A2
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No phenotype data No genotype data No literature annotations Not annotated
SLC8A3
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Pathways

Non-Curated Information

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

Metabolizing Enzymes

Drug Targets

PharmGKB Curated Pathways

Non-Curated Information

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

Drug Interactions

amprenavir Amprenavir increases the effect and toxicity of pimozide
aprepitant Increased risk of cardiotoxicity and arrhythmias
atazanavir The protease inhibitor increases the effect and toxicity of pimozide
citalopram The SSRI increases the effect and toxicity of pimozide
clarithromycin Increased risk of cardiotoxicity and arrhythmias
donepezil Possible antagonism of action
erythromycin Increased risk of cardiotoxicity and arrhythmias
escitalopram The SSRI increases the effect and toxicity of pimozide
fluconazole Increased risk of cardiotoxicity and arrhythmias
fosamprenavir Amprenavir increases the effect and toxicity of pimozide
galantamine Possible antagonism of action
imatinib Imatinib increases the effect and toxicity of pimozide
indinavir The protease inhibitor increases the effect and toxicity of pimozide
itraconazole Increased risk of cardiotoxicity and arrhythmias
josamycin Increased risk of cardiotoxicity and arrhythmias
ketoconazole Increased risk of cardiotoxicity and arrhythmias
mesoridazine Increased risk of cardiotoxicity and arrhythmias
nefazodone increases the effect and toxicity of pimozide
nelfinavir Nelfinavir increases the effect and toxicity of pimozide
paroxetine Increased risk of cardiotoxicity/arrhythmias
posaconazole Contraindicated co-administration
ritonavir The protease inhibitor increases the effect and toxicity of pimozide
rivastigmine Possible antagonism of action
saquinavir The protease inhibitor increases the effect and toxicity of pimozide
sertraline The SSRI increases the effect and toxicity of pimozide
telithromycin Increased risk of cardiotoxicity and arrhythmias
thioridazine Increased risk of cardiotoxicity and arrhythmias
troleandomycin Increased risk of cardiotoxicity and arrhythmias
voriconazole Increased risk of cardiotoxicity and arrhythmias
zileuton Increased risk of cardiotoxicity and arrhythmias
ziprasidone Increased risk of cardiotoxicity and arrhythmias

Non-Curated Information

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

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

  1. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB01100
KEGG Compound ID:
C07566
KEGG Drug ID:
D00560
PubChem Compound ID:
16362
PubChem Substance ID:
9769

Common Searches

Search PubMed
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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.
The PharmGKB is financially supported by the NIH/ NIGMS and is managed at Stanford University (U01GM61374).
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