:Pipotiazine

{{Drugbox

| IUPAC_name = 10-[3-[4-(2-hydroxyethyl)-1-piperidyl]propyl]-N,N-dimethyl-phenothiazine-2-sulfonamide

| image = Pipotiazine.svg

| image_class = skin-invert-image

| width = 275

| tradename = Piportil

| Drugs.com = {{drugs.com|international|pipotiazine}}

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| legal_AU =

| legal_BR = C1

| legal_BR_comment = {{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}}

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| legal_status = Rx-only

| routes_of_administration = Oral, IM

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| IUPHAR_ligand = 7557

| CAS_number = 39860-99-6

| ATC_prefix = N05

| ATC_suffix = AC04

| PubChem = 62867

| DrugBank = DB01621

| ChemSpiderID = 56598

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = L903J9JPYV

| KEGG = D08385

| ChEMBL = 398880

| C=24 | H=33 | N=3 | O=3 | S=2

| smiles = CN(C)S(=O)(=O)C1=CC2=C(C=C1)SC3=CC=CC=C3N2CCCN4CCC(CC4)CCO

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Pipotiazine (Piportil), also known as pipothiazine, is a typical antipsychotic of the phenothiazine class{{cite journal | vauthors = Bechelli LP, Ruffino-Netto A, Hetem G | title = A double-blind controlled trial of pipotiazine, haloperidol and placebo in recently-hospitalized acute schizophrenic patients | journal = Brazilian Journal of Medical and Biological Research | volume = 16 | issue = 4 | pages = 305–11 | date = December 1983 | pmid = 6143579 }} used in the United Kingdom and other countries for the treatment of schizophrenia.{{drugs.com|international|pipotiazine}} Its properties are similar to those of chlorpromazine. A 2004 systematic review investigated its efficacy for people with schizophrenia:

Summary
class="wikitable" \|+ Pipotiazine palmitate compared to oral antipsychotics for schizophrenia{{cite journal \| vauthors = Dinesh M, David A, Quraishi SN \| title = Depot pipotiazine palmitate and undecylenate for schizophrenia \| journal = The Cochrane Database of Systematic Reviews \| volume = 3 \| issue = 4 \| pages = CD001720 \| date = October 2004 \| pmid = 15495016 \| doi = 10.1002/14651858.CD001720.pub2 \| url = http://www.cochrane.org/CD001720/SCHIZ_depot-pipotiazine-palmitate-and-undecylenate-for-schizophrenia \| pmc = 7025786 }}
Although well-conducted and reported randomized trials are still needed to fully inform practice (no trial data exists reporting hospital and services outcomes, quality of life, satisfaction with care and economics) pipotiazine palmitate is a viable choice for both clinician and person with schizophrenia.
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 outcomes
No important clinical response Follow-up: by 3 week)	There is no clear difference between people given pipotiazine palmitate and those receiving oral antipsychotics. These findings are based on data of low quality.	RR 2.57 (0.76 to 8.63)	Low
Leaving the study early Follow-up: up to 5 weeks	Pipotiazine palmitate may increase the chance of leaving the study early but the difference between people given pipotiazine palmitate and those receiving oral antipsychotics is not clear. These findings are based on data of low quality.	RR 3.85 (0.46 to 32.22)	Low
colspan="4" style="text-align: left;"\| Mental state
Relapse Follow-up: by 18 months)	Pipotiazine palmitate has not more - or less - effect on risk of relapse than oral antipsychotics. These findings are based on data of low quality.	RR 1.55 (0.76 to 3.18)	Low
colspan="4" style="text-align: left;"\| Adverse effects
Tardive dyskinesia	Oral antipsychotic drugs and pipotiazine palmitate carry similar risks of this problematic movement disorder. These findings are based on data of low quality.	RR 1.03 (0.22 to 4.92)	Low
Dystonia	Pipotiazine palmitate may slightly reduce the chance of experiencing this movement disorder but there is no clear difference between people given pipotiazine palmitate and those receiving oral antipsychotics. These findings are based on data of low quality.	RR 0.32 (0.04 to 2.89)	Low

Medical uses

Pipotiazine palmitate is used to treat schizophrenia.{{cite web |title=Piportil® L4 (pipotiazine palmitate) |url=http://products.sanofi.ca/en/piportil-l4.pdf |archive-url=https://web.archive.org/web/20211202083516/http://products.sanofi.ca/en/piportil-l4.pdf |access-date=11 December 2023|archive-date=2021-12-02 }}

Contraindications

Pipotiazine palmitate is contraindicated in people with circulatory collapse (shock), altered states of consciousness, including drug intoxication, or other serious health conditions (liver disease, kidney disease, pheochromocytoma, severe cardiovascular disease, or blood dyscrasias). It is contraindicated in people with severe depression. Pipotiazine palmitate should not be used in people who have a history of allergic reactions to any component of the medicine or to chemically similar medicines (phenothiazines).

Pharmacokinetics

Pipotiazine was available as a long-acting injectable formulation (pipotiazine palmitate). After deep intramuscular injection, pipotiazine palmitate reaches maximum plasma concentration in 7-14 days, has an elimination half-life of 15 days, and reaches steady-state levels after 2 months of usual dosing (given every 4 weeks).{{cite web | vauthors = White J |title=Guidance on the Administration to Adults of Oil-based Depot and other Long-acting Intramuscular Antipsychotic Injections 7th Edition |url=https://www.hpft.nhs.uk/media/6180/guidance-on-im-administration-of-oil-based-depots-and-other-long-acting-antipsychotic-injections-7th-edition.pdf |publisher=www.reach4resource.co.uk |access-date=11 December 2023 |date=July 2022}}

Synthesis

File:Pipotiazine synthesis.svg

The alkylation of 2-Dimethylaminosulfonylphenthiazine [1090-78-4] (1) with 1-Bromo-3-chloropropane (2) gives 10-(3-chloropropyl)-N,N-dimethylphenothiazine-2-sulfonamide [40051-12-5] (3). Alkylation with 4-Piperidineethanol [622-26-4] (4) completes the synthesis of Pipothiazine (5).

History

The long-acting injectable formulation of pipotiazine (pipotiazine palmitate) was withdrawn from all markets globally in March 2015 due to a shortage of the active ingredient.{{cite journal | vauthors = Haddad P, Taylor M, Patel MX, Taylor D | title = Guidance on switching away from Piportil Depot® (pipotiazine palmitate) injection | journal = The British Journal of Psychiatry | volume = 206 | issue = 6 | pages = 521 | date = June 2015 | pmid = 26034183 | doi = 10.1192/bjp.206.6.521 | doi-access = free }}

References

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Category:Dimethylamino compounds

Category:M1 receptor antagonists

Category:M2 receptor antagonists

Category:M3 receptor antagonists

Category:M4 receptor antagonists

Category:M5 receptor antagonists

Category:Phenothiazines

Category:Piperazines

Category:Hydroxyethyl compounds

Category:Sulfonamides

Category:Typical antipsychotics