View source for Periciazine

{{short description|Typical antipsychotic medication}}
{{Drugbox
| Verifiedfields = changed
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 3405M6FD73
| verifiedrevid = 437139007
| IUPAC_name = 10-[3-(4-hydroxypiperidin-1-yl)propyl]-10''H''-phenothiazine-2-carbonitrile
| image = Periciazine.svg
| image_class = skin-invert-image
| width = 260
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 2622-26-6
| CAS_supplemental  =
| ATC_prefix = N05
| ATC_suffix = AC01
| ATC_supplemental  = 
| PubChem = 4747
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 251940
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 31981
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank = DB01608
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 4585
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D01485
| chemical_formula  =
| C=21 | H=23 | N=3 | O=1 | S=1
| smiles = C1CN(CCC1O)CCCN2C3=CC=CC=C3SC4=C2C=C(C=C4)C#N
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C21H23N3OS/c22-15-16-6-7-21-19(14-16)24(18-4-1-2-5-20(18)26-21)11-3-10-23-12-8-17(25)9-13-23/h1-2,4-7,14,17,25H,3,8-13H2
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = LUALIOATIOESLM-UHFFFAOYSA-N
| bioavailability = 
| protein_bound = 
| metabolism = [[Hepatic]] (mostly via conjugation)<ref name = TGA/>
| elimination_half-life = 12 h<ref name = TGA>{{cite web|title=NEULACTIL PRODUCT INFORMATION|work=TGA eBusiness Services|publisher=sanofi-aventis australia pty ltd|date=13 September 2011|access-date=2 November 2013|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-05922-3|format=PDF}}</ref>
| excretion = [[Renal]]<ref name = TGA/>
| pregnancy_AU = C
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category= 
| legal_AU = S4
| legal_BR = C1
| 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=[[Diário Oficial da União]] |language=pt-BR |publication-date=2023-04-04}}</ref>
| legal_CA = Rx-only
| legal_UK = POM
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_status = Rx-only
| routes_of_administration = Oral
| class = [[Typical antipsychotic]]
}}

'''Periciazine''' ([[International Nonproprietary Name|INN]]), also known as '''pericyazine''' ([[British Approved Name|BAN]]) or '''propericiazine''', is a [[drug]] that belongs to the [[phenothiazine]] class of [[typical antipsychotic]]s.

Periciazine is not approved for sale in the [[United States]]. It is commonly sold in [[Canada]], [[Italy]] and [[Russia]] under the tradename '''Neuleptil''' and in [[United Kingdom]] and [[Australia]] under the tradename '''Neulactil'''.<ref name = Martindale>{{cite book|title=Pericyazine|work=Martindale: The Complete Drug Reference|publisher=The Royal Pharmaceutical Society of Great Britain|date=23 September 2011|access-date=2 November 2013|url=http://www.medicinescomplete.com/mc/martindale/current/7082-t.htm}}</ref>

==Medical uses==
The primary uses of periciazine include in the short-term treatment of severe [[anxiety]] or tension and in the maintenance treatment of [[psychotic disorder]]s such as [[schizophrenia]]. There is insufficient evidence to determine whether periciazine is more or less effective than other antipsychotics.<ref name = TGA/> A 2014 [[systematic review]] compared periciazine with typical antipsychotics for schizophrenia:
{| class="wikitable"
|+ Periciazine versus typical antipsychotic for schizophrenia<ref name=Mat2014>{{cite journal | vauthors = Matar HE, Almerie MQ, Makhoul S, Xia J, Humphreys P | title = Pericyazine for schizophrenia | journal = The Cochrane Database of Systematic Reviews | volume = 2014 | issue = 5 | pages = CD007479 | date = May 2014 | pmid = 24825770 | url = http://www.cochrane.org/CD007479/SCHIZ_pericyazine-for-the-treatment-of-schizophrenia | doi = 10.1002/14651858.CD007479.pub2 | doi-access =  | pmc = 11023599 }}</ref>
|-
! Summary
|-
|On the basis of very low quality evidence it is not possible to determine the effects of periciazine in comparison with antipsychotics such as [[chlorpromazine]] or [[trifluoperazine]] for the treatment of schizophrenia. There is some evidence, however, that periciazine may be associated with a higher incidence of [[Extrapyramidal symptoms|extrapyramidal]] side effects than other antipsychotics.<ref name=Mat2014/>
|-
| style="padding:0;" |
{| class="wikitable collapsible collapsed" style="width:100%;"
|-
! scope="col" style="text-align: left;"| Outcome
! scope="col" style="text-align: left;"| Findings in words
! scope="col" style="text-align: left;"| Findings in numbers
! scope="col" style="text-align: left;"| Quality of evidence
|-
! colspan="4" style="text-align: left;"| Global state
|-
| Not improved<br>Follow-up: 6-12 weeks || Periciazine may increase the risk of being 'not improved', but, at present it is not possible to be confident about the difference between people receiving periciazine and those given chlorpromazine or trifluoperazine. Data supporting this finding are very limited.
 || [[Relative risk|RR]] 1.24 (0.93 to 1.66) || [[The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach|Very low]]
|-
! colspan="4" style="text-align: left;"| [[Adverse event|Adverse events]]
|-
| Extrapyramidal side effect<br>Follow-up: 6-12 weeks || Periciazine may reduce the chance of experiencing the movement disorder, compared with chlorpromazine or trifluoperazine, but, at present there is only very limited data supporting this finding.
 || [[Relative risk|RR]] 0.59 (0.38 to 0.89) || [[The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach|Very low]]
|-
! colspan="4" style="text-align: left;"| Leaving the study early
|-
| For any reasons<br>Follow-up: 9-12 weeks || Periciazine may reduce the chance of leaving the study early, but, at present it is not possible to be confident about the difference between the two treatments and data supporting this finding are very limited.
 || [[Relative risk|RR]] 0.46 (0.11 to 1.9) || [[The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach|Very low]]
|-
! colspan="4" style="text-align: left;"| Missing outcomes
|-
| || No study reported any data on outcomes such as relapse, mental state, cost-effectiveness, and information relating to behavior||  || 
|-
|}
|}

Periciazine has also been studied in the treatment of [[opioid dependence]].<ref name="pmid10441864">{{cite journal | vauthors = ((Sivolap IuP)), Savchenkov VA | title = [The use of neuroleptics in treating opiate dependence] | language = ru | journal = Zhurnal Nevrologii I Psikhiatrii imeni S.S. Korsakova | volume = 99 | issue = 6 | pages = 29–34 | year = 1999 | pmid = 10441864 }}</ref>

==Adverse effects==
Periciazine is a rather [[sedation|sedating]] and [[anticholinergic]] [[antipsychotic]], and despite being classed with the typical antipsychotics, its risk of [[extrapyramidal symptoms|extrapyramidal side effects]] is comparatively low.<ref name=eTG>{{cite web|title=Approximate relative frequency (not intensity) of common adverse effects of antipsychotics (Table 8.21) [NB1]|date=February 2013|access-date=2 November 2013|url=http://etg.tg.com.au/conc/desktop/index.htm?id=75114e7800512079b341de7fb82c953c|work=eTherapeutic Guidelines complete|publisher=Therapeutic Guidelines Limited}}{{dead link|date=March 2018 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> It has a relatively high risk of causing [[hyperprolactinaemia]] and a moderate risk of causing [[weight gain]] and [[orthostatic hypotension]].<ref name = eTG/>
==Synthesis==
[[File:Pericyazine synthesis.svg|class=skin-invert-image|thumb|center|500px|[https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-16-0053 Thieme] Patent ({{Highlight|Ex V}}):<ref>FR1212031 idem Robert Jacques Georges, Jacob Robert Michel, {{US patent|3075976}} (1963 to Rhone Poulenc Sa).</ref> ]]

The final step in the synthesis involves the alkylation of 3-(2-cyanophenothiazin-10-yl)propyl 4-methylbenzenesulfonate, [https://pubchem.ncbi.nlm.nih.gov/compound/134990672 CID:134990672] ('''1''') with 4-Piperidinol [5382-16-1] ('''2''') giving Periciazine ('''3''').

== References ==
{{Reflist|2}}

== External links ==
* [https://web.archive.org/web/20060427012310/http://emc.medicines.org.uk/emc/assets/c/html/DisplayDoc.asp?DocumentID=15171 Neulactil - Summary of Product Characteristics] from the electronic Medicines Compendium
* [https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-05922-3] from the [[Therapeutic Goods Administration]].
* [https://web.archive.org/web/20131103071954/http://webprod5.hc-sc.gc.ca/dpd-bdpp/item-iteme.do?pm-mp=00018707] from [[Health Canada]].

{{Antipsychotics}}
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[[Category:4-Hydroxypiperidines]]
[[Category:Conjugated nitriles]]
[[Category:M1 receptor antagonists]]
[[Category:M2 receptor antagonists]]
[[Category:M3 receptor antagonists]]
[[Category:M4 receptor antagonists]]
[[Category:M5 receptor antagonists]]
[[Category:Phenothiazines]]
[[Category:Typical antipsychotics]]