| Revision as of 13:08, 5 December 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 457076302 of page Pimozide for the Chem/Drugbox validation project (updated: ''). |
Latest revision as of 21:53, 16 September 2024 edit 76.174.0.57 (talk) Cat. |
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{{Short description|Chemical compound}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}} |
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{{drugbox |
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{{pp-pc}} |
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{{Use dmy dates|date=November 2017}} |
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{{Use American English|date=November 2017}} |
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| verifiedrevid = 419225254 |
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{{infobox drug |
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| IUPAC_name = 1--<BR>4-piperidinyl]-1,3-dihydro-<BR>2''H''-benzimidazole-2-one |
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| Watchedfields = changed |
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| image = Pimozide skeletal.svg |
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| verifiedrevid = 464206733 |
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| width = 300 |
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| IUPAC_name = 1--4-piperidinyl]-1,3-dihydro-2''H''-benzimidazole-2-one |
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| image = Pimozide.svg |
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| width = 200 |
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| image2 = Pimozide-based-on-xtal-3D-bs-17.png |
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<!--Clinical data--> |
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<!--Clinical data--> |
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| tradename = Orap |
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| tradename = Orap |
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| Drugs.com = {{drugs.com|monograph|pimozide}} |
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| Drugs.com = {{drugs.com|monograph|pimozide}} |
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| MedlinePlus = a686018 |
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| MedlinePlus = a686018 |
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| licence_US = Pimozide |
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| pregnancy_category = Teratogenic data in rats exist : drug should only be used when the benefit clearly exceeds the potential harm to the unborn |
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| pregnancy_AU = B1 |
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| legal_status = Rx-only, not a controlled narcotic |
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| pregnancy_US = C |
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| routes_of_administration = oral only |
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| legal_AU = S4 |
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| legal_BR = C1 |
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| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=] |language=pt-BR |publication-date=2023-04-04}}</ref> |
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| legal_US = Rx-only |
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| routes_of_administration = Oral |
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| class = ] |
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<!--Pharmacokinetic data--> |
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<!--Pharmacokinetic data--> |
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| bioavailability = at least 40 to 50% |
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| bioavailability = 40-50% |
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| metabolism = ], ] and ] |
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| metabolism = hepatic, by cytochrome P450, isoenzymes 3A, and 1A2; metabolites are inactive |
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| elimination_half-life = 2 to 3 days (average in one study 55 hours) |
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| elimination_half-life = 55 hours (adults), 66 hours (children) |
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| excretion = urine, and to a lesser extent in feces |
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| excretion = Urine |
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<!--Identifiers--> |
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<!--Identifiers--> |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 2062-78-4 |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| ATC_prefix = N05 |
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| CAS_number = 2062-78-4 |
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| ATC_suffix = AG02 |
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| ATC_prefix = N05 |
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| PubChem = 16362 |
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| ATC_suffix = AG02 |
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| IUPHAR_ligand = 90 |
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| PubChem = 16362 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| IUPHAR_ligand = 90 |
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| DrugBank = DB01100 |
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| DrugBank_Ref = {{drugbankcite|changed|drugbank}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| DrugBank = DB01100 |
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| ChemSpiderID = 15520 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| ChemSpiderID = 15520 |
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| UNII = 1HIZ4DL86F |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| UNII = 1HIZ4DL86F |
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| KEGG = D00560 |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| ChEBI_Ref = {{ebicite|correct|EBI}} |
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| KEGG = D00560 |
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| ChEBI = 8212 |
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| ChEBI_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEBI = 8212 |
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| ChEMBL = 1423 |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = 1423 |
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<!--Chemical data--> |
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<!--Chemical data--> |
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| C=28 | H=29 | F=2 | N=3 | O=1 |
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|C=28 |H=29 |F=2 |N=3 |O=1 |
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| smiles = Fc1ccc(cc1)C(c2ccc(F)cc2)CCCN5CCC(N4c3ccccc3NC4=O)CC5 |
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| molecular_weight = 461.56 |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| smiles = Fc1ccc(cc1)C(c2ccc(F)cc2)CCCN5CCC(N4c3ccccc3NC4=O)CC5 |
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| InChI = 1/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) |
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| StdInChI = 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) |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = YVUQSNJEYSNKRX-UHFFFAOYSA-N |
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| StdInChI = 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) |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = YVUQSNJEYSNKRX-UHFFFAOYSA-N |
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}} |
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}} |
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'''Pimozide''' (sold under the brand name '''Orap''') is a neuroleptic ] of the ] class. It was discovered at ] in 1963. It has a high potency compared to ] (ratio 50-70:1). On a weight basis it is even more potent than ]. It also has special indication for ] and resistant ]. |
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== Medical uses == |
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Pimozide is used for Tourette syndrome,<ref name="Pimozide_1985"/> and resistant ] (Europe, United States, and Canada) and in Europe for ], chronic ], ], and ].<ref>{{cite book | vauthors = Munro A | date = 1999 | title = Delusional disorder | location = Cambridge | publisher = Cambridge University Press | isbn = 0-521-58180-X }}</ref> |
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== Efficacy == |
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A 2013 ] compared pimozide with other antipsychotics for schizophrenia or related psychoses: Pimozide versus any other antipsychotic<ref name=Mot2013>{{cite journal | vauthors = Mothi M, Sampson S | title = Pimozide for schizophrenia or related psychoses | journal = The Cochrane Database of Systematic Reviews | volume = 11 | issue = 11 | pages = CD001949 | date = November 2013 | pmid = 24194433 | doi = 10.1002/14651858.CD001949.pub3 | url = http://www.cochrane.org/CD001949/SCHIZ_pimozide-for-schizophrenia-or-related-psychoses | url-status = live | df = dmy-all | archive-url = https://web.archive.org/web/20171127123319/http://www.cochrane.org/CD001949/SCHIZ_pimozide-for-schizophrenia-or-related-psychoses | archive-date = 27 November 2017 }}</ref> |
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In one case a series of 33 patients with delusional parasitosis (median age, 60 years), pimozide was prescribed for 24 patients, 18 of whom took the drug. The dose ranged from 1 to 5 mg daily. No information regarding initial dosing was specified, although the dose was continued for 6 weeks prior to tapering. Of those patients receiving pimozide, 61% (11/18) experienced improvement in or full remission of symptoms. The use of pimozide for the treatment of delusional parasitosis is based primarily on data from case series/reports that demonstrate some efficacy in the majority of patients. Currently, ]s such as ] or ] are used as first line treatment. However, patients who experience negative side-effects with the first line medications are typically given pimozide.<ref>{{cite journal | vauthors = Generali JA, Cada DJ | title = Pimozide: parasitosis (delusional) | journal = Hospital Pharmacy | volume = 49 | issue = 2 | pages = 134–135 | date = February 2014 | pmid = 24623867 | pmc = 3940679 | doi = 10.1310/hpj4902-134 }}</ref><ref>{{cite journal | vauthors = Meehan WJ, Badreshia S, Mackley CL | title = Successful treatment of delusions of parasitosis with olanzapine | journal = Archives of Dermatology | volume = 142 | issue = 3 | pages = 352–355 | date = March 2006 | pmid = 16549712 | doi = 10.1001/archderm.142.3.352 | doi-access = }}</ref> |
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== Contraindications == |
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It is contraindicated in individuals with either acquired, congenital or a family history of QT interval prolongation.<ref name = EMC /> Its use is advised against in individuals with people with either a personal or a family history of arrhythmias or ].<ref name = EMC /> Likewise its use is also advised against in individuals with uncorrected ] and ] or clinical significant cardiac disorders (e.g. a recent ] or ].<ref name =EMC /> It is also contraindicated in individuals being cotreated with ] (SSRI) or in those with a known hypersensitivity to pimozide or other diphenylbutyl-piperidine derivatives.<ref name = EMC /> Likewise its use is contraindicated in individuals receiving treatment with ], ], or ] inhibitors.<ref name = EMC /> |
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== Side effects == |
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Very common (>10% frequency) side effects include:<ref name = MSR /><ref name = EMC /><ref name = MD /><ref name = DM /> |
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* ] |
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* Constipation |
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* Dizziness |
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* Dry mouth |
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* ] |
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* ] |
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* ] |
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* Speech disorder |
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== Overdose == |
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Pimozide overdose presents with severe ], ], ], QT interval prolongation and ventricular arrhythmias including ].<ref name = EMC /> Gastric lavage, establishment of a patent airway and, if necessary, mechanically assisted respiration is the recommended treatment for pimozide overdose.<ref name = EMC /> Cardiac monitoring should be continued for at least 4 days due to the long half-life of pimozide.<ref name = EMC /> |
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== Pharmacology == |
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Pimozide acts as an ] of the ], ], and ] and the ]. It is also a ] ]. |
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Similarly to other typical antipsychotics pimozide has a high affinity for the ] and this likely results in its sexual (due to ]) and extrapyramidal side effects as well as its therapeutic efficacy against the positive symptoms of ].<ref name="Maudsley">{{cite book |isbn = 978-0-470-97948-8 |title = The Maudsley prescribing guidelines in psychiatry | vauthors = Taylor D, Paton C, Shitij K |year = 2012 |publisher = Wiley-Blackwell |location = West Sussex }}</ref> |
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{| class="wikitable sortable" |
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|+ <big>Binding profile</big><ref group = Note>A lower K<sub>i</sub> value indicates a stronger binding</ref> |
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! Protein !! K<sub>i</sub> (nM)<ref>{{cite web |title = PDSP K<sub>i</sub> Database |work = Psychoactive Drug Screening Program (PDSP) | vauthors = Roth BL, Driscol J |author1-link=Bryan Roth|url = http://pdsp.med.unc.edu/pdsp.php |publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health |access-date = 4 December 2013 |date = 12 January 2011 |url-status = dead |archive-url = https://web.archive.org/web/20131108013656/http://pdsp.med.unc.edu/pdsp.php |archive-date = 8 November 2013 |df = dmy-all }}</ref> !! Notes |
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| ] || 650 || |
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| ] || 48.4 || This receptor is believed to be responsible for the atypicality of other antipsychotics like ], ] and ]. Pimozide's affinity towards this receptor is low compared to its affinity for the D<sub>2</sub> receptor and hence this receptor unlikely contributes to its effects to any meaningful extent. |
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| ] || 2,112 || |
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| ] || 71 || |
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| ] || 0.5 || Relatively high affinity for this receptor may explain its supposed antidepressant-like effects in animal models of depression.<ref>{{cite journal | vauthors = Mahesh R, Pandey DK, Bhatt S, Gautam BK |title = Anti-depressant like Effect of Pimozide in Acute and Chronic Animal Models of Depression |journal = Indian Journal of Pharmaceutical Education and Research |volume = 45 |issue = 1 |pages = 46–53 |date = January–March 2011 }}</ref> |
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| ] || 197.7 || Low affinity towards this receptor may explain why pimozide has a lower liability for producing orthostatic hypotension.<ref name = Maudsley /> |
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| ] || 1,593 || |
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| ] || 821 || |
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| ] || 376.5 || |
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| ] || 1,955 || This receptor is believed to be responsible for the interference with glucose ] seen with some of the ] such as ] and ].<ref name="GG">{{cite book |isbn = 978-0-07-162442-8 |title = Goodman and Gilman's The Pharmacological Basis of Therapeutics |edition = 12th | vauthors = Brunton L, Chabner B, Knollman B |year = 2010 |publisher = McGraw-Hill Professional |location = New York |title-link = Goodman and Gilman's The Pharmacological Basis of Therapeutics }}</ref> Pimozide's low affinity for this receptor likely contributes to the comparatively mild effects on glucose homeostasis. |
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| ] || >10,000 || |
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| ] || 0.33 || Likely the receptor responsible for the therapeutic effects against the positive symptoms of schizophrenia of antipsychotics like pimozide as well as the prolactin-elevating and extrapyramidal side effect-generating effects of typical antipsychotics like pimozide.<ref name = GG /> |
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| ] || 0.25 || |
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| ] || 1.8 || |
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| ] || 18 || May be responsible for pimozide's high liability for prolonging the QT interval.<ref name = GG /> |
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| ] || 692 || Likely responsible for why pimozide tends to produce so little sedation.<ref name =" GG" /> |
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| ] || 508 || |
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{| class="wikitable" align="left" |
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|+ <big>Pharmacokinetic data</big><ref name=MSR>{{cite web |title = Oral (pimozide) dosing, indications, interactions, adverse effects, and more |work = Medscape Reference |publisher = WebMD |access-date = 4 December 2013 |url = http://reference.medscape.com/drug/orap-pimozide-342982#showall |url-status = live |archive-url = https://web.archive.org/web/20131204215602/http://reference.medscape.com/drug/orap-pimozide-342982#showall |archive-date = 4 December 2013 |df = dmy-all }}</ref><ref name=EMC>{{cite web |title = Oral 4 mg tablets. - Summary of Product Characteristics |work = electronic Medicines Compendium |publisher = Janssen-Cilag Ltd |date = 2 April 2013 |access-date = 4 December 2013 |url = http://www.medicines.org.uk/emc/medicine/6753/SPC/Orap+4+mg+tablets./ |url-status = dead |archive-url = https://web.archive.org/web/20160303230421/http://www.medicines.org.uk/emc/medicine/6753/SPC/Orap+4+mg+tablets./ |archive-date = 3 March 2016 }}</ref><ref name = MD>{{cite book |title = Pimozide | vauthors = Brayfield A |work = Martindale: The Complete Drug Reference |publisher = Pharmaceutical Press |location = London, UK |url = https://www.medicinescomplete.com/mc/martindale/current/7087-n.htm |access-date = 4 December 2013 |date = 12 February 2013 }}</ref><ref name=DM>{{cite web |title = ORAP (pimozide) tablet |work = DailyMed |publisher = Teva Select Brands |date = July 2012 |url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=fd9729c3-545f-4d34-9bc7-72b61e028fc4 |access-date = 4 December 2013 |url-status = live |archive-url = https://web.archive.org/web/20130703154327/http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=fd9729c3-545f-4d34-9bc7-72b61e028fc4 |archive-date = 3 July 2013 |df = dmy-all }}</ref> |
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! Pharmacokinetic parameter !! Value |
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| Time to peak plasma concentration (T<sub>max</sub>) || 6-8 hr |
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| Peak plasma concentration (C<sub>max</sub>) || 4-19 ng/mL |
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| Elimination half-life (t<sub>1/2</sub>) || 55 hours (adults), 66 hours (children) |
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| Metabolising enzymes || ], ] and ] |
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| Excretion pathways || Urine |
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{{clear}} |
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== History == |
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In 1985 pimozide was approved by the FDA for marketing as an ] for the treatment of Tourette's syndrome.<ref name="Pimozide_1985">{{cite journal | vauthors = Colvin CL, Tankanow RM | title = Pimozide: use in Tourette's syndrome | journal = Drug Intelligence & Clinical Pharmacy | volume = 19 | issue = 6 | pages = 421–424 | date = June 1985 | pmid = 3891283 | doi = 10.1177/106002808501900602 | s2cid = 19179304 }}</ref> |
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== See also == |
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{{Portal|Medicine}} |
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* ] |
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* ] |
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* ] |
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* ] |
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== Notes == |
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{{reflist|group=Note}} |
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== References == |
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{{Reflist}} |
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== External links == |
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{{Antipsychotics}} |
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