PIMOZIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C28H29F2N3O
Molecular Weight	461.5462
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

FC1=CC=C(C=C1)C(CCCN2CCC(CC2)N3C(=O)NC4=C3C=CC=C4)C5=CC=C(F)C=C5

InChI

InChIKey=YVUQSNJEYSNKRX-UHFFFAOYSA-N

InChI=1S/C28H29F2N3O/c29-22-11-7-20(8-12-22)25(21-9-13-23(30)14-10-21)4-3-17-32-18-15-24(16-19-32)33-27-6-2-1-5-26(27)31-28(33)34/h1-2,5-14,24-25H,3-4,15-19H2,(H,31,34)

HIDE SMILES / InChI

Molecular Formula	C28H29F2N3O
Molecular Weight	461.5462
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/017473s046lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/10762666

Pimozide (Orap) is 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. It is not intended as a treatment of first choice nor is it intended for the treatment of tics that are merely annoying or cosmetically troublesome. It should be reserved for use in Tourette’s Disorder patients whose development and/or daily life function is severely compromised by the presence of motor and phonic tics. Evidence supporting approval of pimozide for use in Tourette’s Disorder was obtained in two controlled clinical investigations, which enrolled patients between the ages of 8 and 53 years. Most subjects in the two trials were 12 or older. 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. Although its exact mode of action has not been established, the ability of pimozide to suppress motor and phonic tics in Tourette’s Disorder is thought to be a function of its dopaminergic blocking activity. 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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
HERG 99 Target ID: CHEMBL240 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11511086	Inhibitor 8504		18.0 nM [IC50]
Dopamine receptor 60 Target ID: CHEMBL2096905 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8301582	Antagonist 2849

Conditions

Condition	Modality	Targets	Highest Phase	Product
Tourette's syndrome 20 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/017473s046lbl.pdf	Palliative		Approved 8583	ORAP Approved Use INDICATIONS & USAGE Pimozide Tablets, USP is indicated for the suppression of motor and phonic tics in patients with Tourette’s Disorder who have failed to respond satisfactorily to standard treatment. Pimozide Tablets, USP is not intended as a treatment of first choice nor is it intended for the treatment of tics that are merely annoying or cosmetically troublesome. Pimozide Tablets, USP should be reserved for use in Tourette’s Disorder patients whose development and/or daily life function is severely compromised by the presence of motor and phonic tics. Evidence supporting approval of Pimozide Tablets, USP for use in Tourette’s Disorder was obtained in two controlled clinical investigations which enrolled patients between the ages of 8 and 53 years. Most subjects in the two trials were 12 or older. Launch Date 1984

AUC

Value	Dose	Co-administered	Analyte	Population
0.261 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3480904	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		PIMOZIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.347 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3480904	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		PIMOZIDE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
109 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3480904	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		PIMOZIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
57 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3480904	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		PIMOZIDE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
6 mg 1 times / day single, oral Overdose Dose: 6 mg, 1 times / day Route: oral Route: single Dose: 6 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15641643/	healthy, 1.5 Health Status: healthy Age Group: 1.5 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/15641643/	Other AEs: Tremor, Tongue thrust... Other AEs: Tremor Tongue thrust Drooling Drowsiness Slow response to stimuli Blood pressure decreased Sources: https://pubmed.ncbi.nlm.nih.gov/15641643/
100 mg 1 times / day single, oral Overdose Dose: 100 mg, 1 times / day Route: oral Route: single Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/824116/	healthy, 17 Health Status: healthy Age Group: 17 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/824116/	Other AEs: Tremor... Other AEs: Tremor Sources: https://pubmed.ncbi.nlm.nih.gov/824116/
0.2 mg/kg 1 times / day multiple, oral Recommended Dose: 0.2 mg/kg, 1 times / day Route: oral Route: multiple Dose: 0.2 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6371107/	unhealthy, 2-13 Health Status: unhealthy Age Group: 2-13 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/6371107/	Disc. AE: Akathisia, Akinesia... AEs leading to discontinuation/dose reduction: Akathisia Akinesia Sources: https://pubmed.ncbi.nlm.nih.gov/6371107/
800 mg 1 times / day single, oral Overdose Dose: 800 mg, 1 times / day Route: oral Route: single Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15641643/	healthy, 53 Health Status: healthy Age Group: 53 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/15641643/	Other AEs: Torsades de pointes, Electrocardiogram QTc interval prolonged... Other AEs: Torsades de pointes Electrocardiogram QTc interval prolonged Sources: https://pubmed.ncbi.nlm.nih.gov/15641643/
21 mg 1 times / day multiple, oral Highest studied dose Dose: 21 mg, 1 times / day Route: oral Route: multiple Dose: 21 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/4214674/	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/4214674/	Sources: https://pubmed.ncbi.nlm.nih.gov/4214674/

AEs

AE	Significance	Dose	Population
Blood pressure decreased		6 mg 1 times / day single, oral Overdose Dose: 6 mg, 1 times / day Route: oral Route: single Dose: 6 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15641643/	healthy, 1.5 Health Status: healthy Age Group: 1.5 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/15641643/
Drooling		6 mg 1 times / day single, oral Overdose Dose: 6 mg, 1 times / day Route: oral Route: single Dose: 6 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15641643/	healthy, 1.5 Health Status: healthy Age Group: 1.5 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/15641643/
Drowsiness		6 mg 1 times / day single, oral Overdose Dose: 6 mg, 1 times / day Route: oral Route: single Dose: 6 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15641643/	healthy, 1.5 Health Status: healthy Age Group: 1.5 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/15641643/
Slow response to stimuli		6 mg 1 times / day single, oral Overdose Dose: 6 mg, 1 times / day Route: oral Route: single Dose: 6 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15641643/	healthy, 1.5 Health Status: healthy Age Group: 1.5 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/15641643/
Tongue thrust		6 mg 1 times / day single, oral Overdose Dose: 6 mg, 1 times / day Route: oral Route: single Dose: 6 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15641643/	healthy, 1.5 Health Status: healthy Age Group: 1.5 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/15641643/
Tremor		6 mg 1 times / day single, oral Overdose Dose: 6 mg, 1 times / day Route: oral Route: single Dose: 6 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15641643/	healthy, 1.5 Health Status: healthy Age Group: 1.5 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/15641643/
Tremor		100 mg 1 times / day single, oral Overdose Dose: 100 mg, 1 times / day Route: oral Route: single Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/824116/	healthy, 17 Health Status: healthy Age Group: 17 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/824116/
Akathisia	Disc. AE	0.2 mg/kg 1 times / day multiple, oral Recommended Dose: 0.2 mg/kg, 1 times / day Route: oral Route: multiple Dose: 0.2 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6371107/	unhealthy, 2-13 Health Status: unhealthy Age Group: 2-13 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/6371107/
Akinesia	Disc. AE	0.2 mg/kg 1 times / day multiple, oral Recommended Dose: 0.2 mg/kg, 1 times / day Route: oral Route: multiple Dose: 0.2 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6371107/	unhealthy, 2-13 Health Status: unhealthy Age Group: 2-13 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/6371107/
Electrocardiogram QTc interval prolonged		800 mg 1 times / day single, oral Overdose Dose: 800 mg, 1 times / day Route: oral Route: single Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15641643/	healthy, 53 Health Status: healthy Age Group: 53 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/15641643/
Torsades de pointes		800 mg 1 times / day single, oral Overdose Dose: 800 mg, 1 times / day Route: oral Route: single Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15641643/	healthy, 53 Health Status: healthy Age Group: 53 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/15641643/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946		substrate 1388

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741 L-type Ca2+ channels 28 T-type Ca2+ channels 3	CYP1A2 1197 P-gp 2052

Drug as perpetrator

Target	Modality	Activity
L-type Ca2+ channels 30	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/2160063/	yes
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/30275188/	yes
T-type Ca2+ channels 3	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/29202456/	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/017473Orig1s046.pdf Page: 9, 15	major
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/017473Orig1s046.pdf Page: 9.0	minor
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/017473Orig1s046.pdf Page: 9, 10, 15	minor	yes (co-administration study) Comment: coadministration with paroxetine resulted in a 151% increase in pimozide AUC and 62% increase in pimozide Cmax. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/017473Orig1s046.pdf Page: 9, 10, 15
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/33119612/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:8212	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:8212
ChemicalBook	CB7290660	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7290660
eMolecules	593283	https://www.emolecules.com/cgi-bin/more?vid=593283
MolPort	MolPort-001-736-597	https://www.molport.com/shop/molecule-link/MolPort-001-736-597
ZINC	ZINC000004175630	http://zinc15.docking.org/substances/ZINC000004175630

PubMed

Title	Date	PubMed
Tic reduction with risperidone versus pimozide in a randomized, double-blind, crossover trial.	2004-02	14726728
T-type calcium channels in the regulation of afferent and efferent arterioles in rats.	2004-02	14583435
Zebrafish embryos express an orthologue of HERG and are sensitive toward a range of QT-prolonging drugs inducing severe arrhythmia.	2003-12-15	14678746
Effects of imatinib mesylate (STI571, Glivec) on the pharmacokinetics of simvastatin, a cytochrome p450 3A4 substrate, in patients with chronic myeloid leukaemia.	2003-11-17	14612892
Cav3.1 (alpha1G) T-type Ca2+ channels mediate vaso-occlusion of sickled erythrocytes in lung microcirculation.	2003-08-22	12869394
Inhibitory effects of pimozide on cloned and native voltage-gated potassium channels.	2003-07-04	12824052
Antipsychotic medication and seizures: a review.	2003-07	12973403
[A case of delusional parasitosis in severe heart failure. Olanzapine within the framework of a multimodal therapy].	2003-07	12861369
Pimozide injections into the Nucleus accumbens disrupt maternal behaviour in lactating rats.	2003-07	12828573
Cannabinoid pharmacological properties common to other centrally acting drugs.	2003-06-27	12826237
Disabling cough: habit disorder or tic syndrome?	2003-06-07	12801773
Disabling cough: habit disorder or tic syndrome?	2003-06-07	12801772
Cytotoxicity of conventional and atypical antipsychotic drugs in relation to glucose metabolism.	2003-05-02	12691834
8-[3H]-hydroxy-2-(di-n-propylamino)tetralin binding sites in blood lymphocytes of rats and the modulation by mitogens and immobilization.	2003-05	12742647
Delusional parasitosis in leprosy.	2003-04-24	12708735
Noradrenergic modulation of ephedrine-induced hypophagia.	2003-04	12557268
Detection of proarrhythmia in the female rabbit heart: blinded validation.	2003-03	12716112
Screening, library-assisted identification and validated quantification of fifteen neuroleptics and three of their metabolites in plasma by liquid chromatography/mass spectrometry with atmospheric pressure chemical ionization.	2003-03	12644990
Pimozide: use in dermatology.	2003-03	12639456
H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs.	2003-03	12629531
Biphasic role of dopamine on female sexual behaviour via D2 receptors in the mediobasal hypothalamus.	2003-03	12604086
A boy with a disabling cough.	2003-02-22	12606180
[A child with peculiar movements: Sydenham chorea].	2003-02-08	12621982
P300 changes in major depressive disorders with and without psychotic features.	2003-02	12547298
Antipsychotic augmentation for treatment resistant obsessive-compulsive disorder: what if antipsychotic is discontinued?	2003-01	12490771
[Chronic tic disorders--chronic mortor or vocal tic disorders and de la Tourette's syndrome].	2003	14626066
QTc prolongation due to propranolol overdose.	2003	12968835
Drug interactions of clinical significance for the dermatologist: recognition and avoidance.	2003	12926981
Lopinavir/ritonavir: a review of its use in the management of HIV infection.	2003	12662125
Corticotropin-releasing factor as well as opioid and dopamine are involved in tail-pinch-induced food intake of rats.	2003	12559107
The effects of long-term testosterone, gonadotropin-releasing hormone agonist and pimozide treatments on testicular development and luteinizing hormone levels in juvenile and early maturing striped bass, Morone saxatilis.	2002-12	12460602
Obesity and related metabolic abnormalities during antipsychotic drug administration: mechanisms, management and research perspectives.	2002-11	12518268
The role of nutrition in the regulation of LH secretion during anestrus by the serotoninergic and dopaminergic systems in Mediterranean ewes treated with melatonin.	2002-10-15	12387344
[Delusions of parasitosis: An up-to-date review].	2002-10	12376915
Na(+)/Ca(2+) exchanger in porcine oocytes.	2002-10	12297528
[False parasitic diseases].	2002-09-07	12214530
[Tic syndrome].	2002-08-21	12185806
A comparison of the receptor binding and HERG channel affinities for a series of antipsychotic drugs.	2002-08-16	12176106
[Treatment of tics in Tourette syndrome with atypical antipsychotic drugs].	2002-08-05	12362607
Influence of GnRH agonist and neural antagonists on stress-blockade of LH and prolactin surges induced by 17beta-estradiol in ovariectomized rats.	2002-08	12205737
The Ca(2+) channel antagonists mibefradil and pimozide inhibit cell growth via different cytotoxic mechanisms.	2002-08	12130671
The treatment of Tourette's syndrome: current opinions.	2002-07	12083990
Potassium channel antagonists influence porcine granulosa cell proliferation, differentiation, and apoptosis.	2002-07	12080003
Trigeminal neuralgia.	2002-06	12230739
Neuroleptic withdrawal versus serotonergic syndrome in an 8-year-old child.	2002	12427301
Antipsychotic-related QTc prolongation, torsade de pointes and sudden death.	2002	12109926
Use of pimozide in the Pisa syndrome.	1992-08	1322069
Pharmacology of human dopamine D3 receptor expressed in a mammalian cell line: comparison with D2 receptor.	1992-04-10	1354163
Pimozide-induced depression associated with polyuria and polydipsia.	1992-04	1307220
Ascending catecholamine pathways and amphetamine-induced locomotor activity: importance of dopamine and apparent non-involvement of norepinephrine.	1975-08-15	1236760

Patents

Sample Use Guides

In Vivo Use Guide

Children: Treatment should be initiated at a dose of 0.05 mg/kg preferably taken once at bedtime. The dose may be increased every third day to a maximum of 0.2 mg/kg not to exceed 10 mg/day. Adults: treatment should be initiated with a dose of 1 to 2 mg a day in divided doses. The dose may be increased thereafter every other day. Most patients are maintained at less than 0.2 mg/kg/day, or 10 mg/day, whichever is less. Doses greater than 0.2 mg/kg/day or 10 mg/day are not recommended. At doses above 4 mg/day, CYP 2D6 genotyping should be performed. In poor CYP 2D6 metabolizers, doses should not exceed 4 mg/day, and doses should not be increased earlier than 14 days.

Route of Administration: Oral

In Vitro Use Guide

Pimozide (PMZD) (10 uM) had minimal effect on Kv1.4, and had no effect on the M-current candidates, KCNQ2 and KCNQ3 when co-expressed in Xenopus oocytes. In hippocampal neurons, PMZD inhibited the delayed rectifiers by approximately 60%, and A-type currents were insensitive to PMZD. The results suggest that PMZD inhibits certain neuronal Kv channels in heterologous expression systems and in hippocampal neurons. PMZD was less effective on A-type currents, presumably because its ability to block requires a prolonged opening of the K channels.

Substance Class	Chemical Created by `admin` on `Wed Apr 02 09:13:54 GMT 2025` Edited by `admin` on `Wed Apr 02 09:13:54 GMT 2025`
Record UNII	1HIZ4DL86F
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ORAP

Preferred Name

English

PIMOZIDE

Official Name

English

PIMOZIDE [USP MONOGRAPH]

Common Name

English

PIMOZIDE [ORANGE BOOK]

Common Name

English

MCN-JR-6238

Code

English

Pimozide [WHO-DD]

Common Name

English

2H-BENZIMIDAZOL-2-ONE, 1-(1-(4,4-BIS(4-FLUOROPHENYL)BUTYL)-4-PIPERIDINYL)-1,3-DIHYDRO

Common Name

English

PIMOZIDE [USAN]

Common Name

English

NSC-170984

Code

English

PIMOZIDE [MART.]

Common Name

English

PIMOZIDE [JAN]

Common Name

English

PIMOZIDE [EP MONOGRAPH]

Common Name

English

pimozide [INN]

Common Name

English

1-[1-[4,4-Bis(4-fluorophenyl)butyl]-4-piperidyl]-2-benzimidazolinone

Systematic Name

English

R 623

Code

English

PIMOZIDE [MI]

Common Name

English

PIMOZIDE [VANDF]

Common Name

English

R-6238

Code

English

PIMOZIDE [USP-RS]

Common Name

English

R-623

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C29710