Pimozide

Các tên gọi khác (7 ) :

Halomonth
Neoperidole
Opiran
Orap
Pimozida
Pimozide
Pimozidum

Thuốc chống rối loạn tâm thần

Thuốc Gốc

Small Molecule

CAS: 2062-78-4

ATC: N05AG02

ĐG : Gate Pharmaceuticals

CTHH: C₂₈H₂₉F₂N₃O

PTK: 461.5462

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)

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₂₈H₂₉F₂N₃O

Phân tử khối

461.5462

Monoisotopic mass

461.227868975

InChI

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)

InChI Key

InChIKey=YVUQSNJEYSNKRX-UHFFFAOYSA-N

IUPAC Name

1-{1-[4,4-bis(4-fluorophenyl)butyl]piperidin-4-yl}-2,3-dihydro-1H-1,3-benzodiazol-2-one

Traditional IUPAC Name

pimozide

SMILES

FC1=CC=C(C=C1)C(CCCN1CCC(CC1)N1C(=O)NC2=CC=CC=C12)C1=CC=C(F)C=C1

Độ tan chảy

214-218 °C

Độ hòa tan

10 mg/L (at 25 °C)

logP

6.30

logS

-5.4

pKa (strongest acidic)

12.9

pKa (Strongest Basic)

8.38

PSA

35.58 Å²

Refractivity

132.21 m³·mol^-1

Polarizability

50.04 Å³

Rotatable Bond Count

H Bond Acceptor Count

H Bond Donor Count

Physiological Charge

Number of Rings

Bioavailability

MDDR-Like Rule

true

pKa

8.63

Dược Lực Học : 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).

Cơ Chế Tác Dụng : 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) 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.

Dược Động Học :

▧ Absorption :
Greater than 50% absorption after oral administration. Serum peak appears 6-8 hours post ingestion.
▧ Metabolism :
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).

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

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

Tương Tác Thuốc :

Amprenavir Amprenavir may increase the effect and toxicity of pimozide.
Aprepitant Increased risk of cardiotoxicity and arrhythmias
Artemether Additive QTc-prolongation may occur. Concomitant therapy is contraindicated.
Atazanavir The protease inhibitor, atazanavir, may increase the effect and toxicity of pimozide.
Boceprevir Boceprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
Citalopram The SSRI, citalopram, may increase 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, escitalopram, 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 may increase the effect and toxicity of pimozide.
Indinavir The protease inhibitor, indinavir, may increase 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
Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy is contraindicated.
Mesoridazine Increased risk of cardiotoxicity and arrhythmias
Nefazodone Nefazodone may increase the effect and toxicity of pimozide.
Nelfinavir Nelfinavir increases the effect and toxicity of pimozide
Paroxetine Increased risk of cardiotoxicity and arrhythmias.
Posaconazole Contraindicated co-administration
Ritonavir The protease inhibitor, ritonavir, may increase the effect and toxicity of pimozide.
Rivastigmine Possible antagonism of action
Saquinavir The protease inhibitor, saquinavir, may increase the effect and toxicity of pimozide.
Sertraline The SSRI, sertraline, increases the effect and toxicity of pimozide.
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.
Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Telaprevir Telaprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
Telavancin Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Telithromycin Telithromycin may reduce clearance of Pimozide. Concomitant therapy is contraindicated.
Tetrabenazine May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
Thioridazine 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.
Ticlopidine Avoid combination with pimozide and other major CYP3A4 substrates due to the potential increase of pimozide concentration.
Tipranavir Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Pimozide. Concomitant therapy is contraindicated.
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.
Trimethobenzamide Trimethobenzamide and Pimozide, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Trimipramine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
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.
Troleandomycin Increased risk of cardiotoxicity and arrhythmias
Trospium Trospium and Pimozide, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
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.
Vorinostat Additive QTc prolongation may occur. Concomitant therapy is contraindicated.
Zileuton Increased risk of cardiotoxicity and arrhythmias
Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.
Zuclopenthixol Additive QTc-prolonging effects increases risk of cardiac arrhythmias. Concomitant therapy is contraindicated.

Liều Lượng & Cách Dùng : Tablet - Oral

Dữ Kiện Thương Mại

Giá thị trường

Biệt dược thương mại : Orap 2 mg tablet

Giá bán buôn : USD >1.17

Đơn vị tính : tablet
Biệt dược thương mại : Orap 1 mg tablet

Giá bán buôn : USD >1.22

Đơn vị tính : tablet
Biệt dược thương mại : Apo-Pimozide 2 mg Tablet

Giá bán buôn : USD >0.24

Đơn vị tính : tablet
Biệt dược thương mại : Apo-Pimozide 4 mg Tablet

Giá bán buôn : USD >0.43

Đơn vị tính : tablet
Biệt dược thương mại : Orap 4 mg Tablet

Giá bán buôn : USD >0.47

Đơn vị tính : tablet

Nhà Sản Xuất

Công ty :

Sản phẩm biệt dược : Neoperidole
Công ty :

Sản phẩm biệt dược : Opiran
Công ty :

Sản phẩm biệt dược : Orap

Đóng gói

Công ty : Gate Pharmaceuticals
Công ty : McNeil Laboratories
Công ty : Teva Pharmaceutical Industries Ltd.

Website : http://www.tevapharm.com

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB01100

PubChem Compound

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=16362

PubChem Substance

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46507096

KEGG Compound

http://www.genome.jp/dbget-bin/www_bget?cpd:C07566

KEGG Drug

http://www.genome.jp/dbget-bin/www_bget?drug:D00560

ChemSpider

http://www.chemspider.com/Chemical-Structure.15520.html

PharmGKB

http://www.pharmgkb.org/drug/PA450965

Wikipedia

http://en.wikipedia.org/wiki/Pimozide

RxList

http://www.rxlist.com/cgi/generic3/orap.htm

Drugs.com

http://www.drugs.com/cdi/pimozide.html

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