QuickView for Pimozide (compound)

Summary
General Info

PubChem

PubChem Compound 16362

Name:	Pimozide
PubChem Compound ID:	16362
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)
Molecular formula:	C₂₈H₂₉F₂N₃O
Molecular weight:	461.546 g/mol
Synonyms:	KBio2_006061; NCGC00024888-01; Pimozide [USAN:BAN:INN:JAN]; Lopac-P-1793; Pimozide (JAN/USP); SPBio_001211; NCGC00015802-01; Spectrum3_001451; BRN 0729089; Orap (TN). show more » KBio2_006061; NCGC00024888-01; Pimozide [USAN:BAN:INN:JAN]; Lopac-P-1793; Pimozide (JAN/USP); SPBio_001211; NCGC00015802-01; Spectrum3_001451; BRN 0729089; Orap (TN); 2H-Benzimidazol-2-one, 1-[1-[4, 4-bis (4-fluorophenyl)butyl]-4-piperidinyl]-1,3-dihydro-; CAS-2062-78-4; NINDS_000386; MLS000028410; 2H-Benzimidazol-2-one, 1-(1-(4,4-bis(4-fluorophenyl)butyl)-4-piperidinyl)-1,3-dihydro-; NSC 170984; KBio2_000925; 1-(1-(4,4-Bis(p-fluorophenyl)butyl)-4-piperidyl)-2-benzimidazolinone; 1-[1-[4, 4-Bis(p-fluorophenyl)butyl]-4-piperidyl]-2-benzimidazolinone; D00560; Primozida [INN-Spanish]; Spectrum_000445; KBioSS_000925; KBio3_002441; KBio1_000386; 2062-78-4; NCGC00016601-01; Tocris-0937; SMR000058385; McN-JR-6238; R-6238; Opiran; KBioGR_000720; Pimozide; Prestwick_395; DivK1c_000386; Spectrum4_000420; Spectrum2_001026; NSC170984; Prestwick0_000308; Orap; Prestwick1_000308; NCIMech_000356; 5-24-02-00367 (Beilstein Handbook Reference); EU-0100946; 1-[4, 4-Bis(p-fluorophenyl)butyl]-4-(2-oxo-1-benzimidazolinyl)piperidine; 1-(4,4-Bis(p-fluorophenyl)butyl)-4-(2-oxo-1-benzimidazolinyl)piperidine; R 6238; EINECS 218-171-7; McN-JR 6238; Pimozidum [INN-Latin]; 2H-Benzimidazol-2-one, 1-[1-[4,4-bis(4-fluorophenyl)butyl]-4-piperidinyl]-1,3-dihydro-; KBio2_003493; C07566; SPBio_002495; 2-Benzimidazolinone, 1-[1-[4, 4-bis (p-fluorophenyl)butyl]-4-piperidyl]- show less «

DrugBank

Identification

Name:	Pimozide
Name (isomeric):	DB01100
Drug Type:	small molecule
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)
Synonyms:	Pimozidum [INN-Latin]; Pimozida [INN-Spanish]
Brand:	Halomonth, Neoperidole, Orap, Opiran
Category:	Anti-Dyskinesia Agents, Dopamine Antagonists, Antipsychotic Agents
CAS number:	2062-78-4

Pharmacology

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.
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... show more » 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). show less «
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 and inhibits the dopamine D2 receptor in the CNS.
Absorption:	Greater than 50% absorption after oral administration. Serum peak appears 6-8 hours post ingestion.
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.
Half Life:	29 ± 10 hours (single-dose study of healthy volunteers).
Toxicity:	LD₅₀ = 1100 mg/kg (rat, oral), 228 mg/kg (mouse, oral)
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Grapefruit and grapefruit juice should be avoided throughout treatment. Grapefruit can increase serum levels of this product.

Take without regard to meals.

Drug interaction:

Fluconazole	Increased risk of cardiotoxicity and arrhythmias
Erythromycin	Increased risk of cardiotoxicity and arrhythmias
Sertraline	The SSRI, sertraline, increases the effect and toxicity of pimozide.
Tetrabenazine	May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
Tacrine	The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Pimozide, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.

Fluconazole	Increased risk of cardiotoxicity and arrhythmias
Erythromycin	Increased risk of cardiotoxicity and arrhythmias
Sertraline	The SSRI, sertraline, increases the effect and toxicity of pimozide.
Tetrabenazine	May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
Tacrine	The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Pimozide, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
Troleandomycin	Increased risk of cardiotoxicity and arrhythmias
Paroxetine	Increased risk of cardiotoxicity and arrhythmias.
Escitalopram	The SSRI, escitalopram, increases the effect and toxicity of pimozide.
Vorinostat	Additive QTc prolongation may occur. Concomitant therapy is contraindicated.
Telithromycin	Telithromycin may reduce clearance of Pimozide. Concomitant therapy is contraindicated.
Donepezil	Possible antagonism of action
Zileuton	Increased risk of cardiotoxicity and arrhythmias
Amprenavir	Amprenavir may increase the effect and toxicity of pimozide.
Saquinavir	The protease inhibitor, saquinavir, may increase the effect and toxicity of pimozide.
Josamycin	Increased risk of cardiotoxicity and arrhythmias
Nefazodone	Nefazodone may increase the effect and toxicity of pimozide.
Ziprasidone	Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.
Ketoconazole	Increased risk of cardiotoxicity and arrhythmias
Artemether	Additive QTc-prolongation may occur. Concomitant therapy is contraindicated.
Mesoridazine	Increased risk of cardiotoxicity and arrhythmias
Clarithromycin	Increased risk of cardiotoxicity and arrhythmias
Thiothixene	May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Thioridazine	Increased risk of cardiotoxicity and arrhythmias
Itraconazole	Increased risk of cardiotoxicity and arrhythmias
Voriconazole	Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of pimozide by decreasing its metabolism. Increased risk of QTc prolongation and development arrhythmias. Concomitant use is contraindicated.
Tipranavir	Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Pimozide. Concomitant therapy is contraindicated.
Galantamine	Possible antagonism of action
Fosamprenavir	Amprenavir increases the effect and toxicity of pimozide
Citalopram	The SSRI, citalopram, may increase the effect and toxicity of pimozide.
Nelfinavir	Nelfinavir increases the effect and toxicity of pimozide
Lumefantrine	Additive QTc-prolongation may occur. Concomitant therapy is contraindicated.
Trimethobenzamide	Trimethobenzamide and Pimozide, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Tacrolimus	Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Imatinib	Imatinib may increase the effect and toxicity of pimozide.
Posaconazole	Contraindicated co-administration
Toremifene	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Atazanavir	The protease inhibitor, atazanavir, may increase the effect and toxicity of pimozide.
Indinavir	The protease inhibitor, indinavir, may increase the effect and toxicity of pimozide.
Triprolidine	Triprolidine and Pimozide, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
Trimipramine	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Aprepitant	Increased risk of cardiotoxicity and arrhythmias
Zuclopenthixol	Additive QTc-prolonging effects increases risk of cardiac arrhythmias. Concomitant therapy is contraindicated.
Trospium	Trospium and Pimozide, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Rivastigmine	Possible antagonism of action
Ritonavir	The protease inhibitor, ritonavir, may increase the effect and toxicity of pimozide.

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Targets

D(2) dopamine receptor

D(3) dopamine receptor

Potassium voltage-gated channel subfamily H member 2

Enzymes

Transporters

Multidrug resistance protein 1