# Pipotiazine

Pipotiazine (Piportil), also known as pipothiazine, is a typical antipsychotic of the phenothiazine class used in the United Kingdom and other countries for the treatment of schizophrenia. Its properties are similar to those of chlorpromazine. A 2004 systematic review investigated its efficacy for people with schizophrenia:
Summary :
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. :
| Outcome | Findings in words | Findings in numbers | Quality of evidence |
| 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 |
| 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 |
| 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 |
vte Pharmacokinetics of long-acting injectable antipsychotics :
| Medication | Brand name | Class | Vehicle | Dosage | T$_{max}$ | t$_{1/2}$ single | t$_{1/2}$ multiple | logP$^c$ |
| Aripiprazole lauroxil | Aristada | Atypical | Water$^a$ | 441–1064 mg/4–8 weeks | 24–35 days | ? | 54–57 days | 7.9–10.0 |
| Aripiprazole monohydrate | Abilify Maintena | Atypical | Water$^a$ | 300–400 mg/4 weeks | 7 days | ? | 30–47 days | 4.9–5.2 |
| Bromperidol decanoate | Impromen Decanoas | Typical | Sesame oil | 40–300 mg/4 weeks | 3–9 days | ? | 21–25 days | 7.9 |
| Clopentixol decanoate | Sordinol Depot | Typical | Viscoleo$^b$ | 50–600 mg/1–4 weeks | 4–7 days | ? | 19 days | 9.0 |
| Flupentixol decanoate | Depixol | Typical | Viscoleo$^b$ | 10–200 mg/2–4 weeks | 4–10 days | 8 days | 17 days | 7.2–9.2 |
| Fluphenazine decanoate | Prolixin Decanoate | Typical | Sesame oil | 12.5–100 mg/2–5 weeks | 1–2 days | 1–10 days | 14–100 days | 7.2–9.0 |
| Fluphenazine enanthate | Prolixin Enanthate | Typical | Sesame oil | 12.5–100 mg/1–4 weeks | 2–3 days | 4 days | ? | 6.4–7.4 |
| Fluspirilene | Imap, Redeptin | Typical | Water$^a$ | 2–12 mg/1 week | 1–8 days | 7 days | ? | 5.2–5.8 |
| Haloperidol decanoate | Haldol Decanoate | Typical | Sesame oil | 20–400 mg/2–4 weeks | 3–9 days | 18–21 days | 18–21 days | 7.2–7.9 |
| Olanzapine pamoate | Zyprexa Relprevv | Atypical | Water$^a$ | 150–405 mg/2–4 weeks | 7 days | ? | 30 days | – |
| Oxyprothepin decanoate | Meclopin | Typical | ? | ? | ? | ? | ? | 8.5–8.7 |
| Paliperidone palmitate | Invega Sustenna | Atypical | Water$^a$ | 39–819 mg/4–12 weeks | 13–33 days | 25–139 days | ? | 8.1–10.1 |
| Perphenazine decanoate | Trilafon Dekanoat | Typical | Sesame oil | 50–200 mg/2–4 weeks | ? | ? | 27 days | 8.9 |
| Perphenazine enanthate | Trilafon Enanthate | Typical | Sesame oil | 25–200 mg/2 weeks | 2–3 days | ? | 4–7 days | 6.4–7.2 |
| Pipotiazine palmitate | Piportil Longum | Typical | Viscoleo$^b$ | 25–400 mg/4 weeks | 9–10 days | ? | 14–21 days | 8.5–11.6 |
| Pipotiazine undecylenate | Piportil Medium | Typical | Sesame oil | 100–200 mg/2 weeks | ? | ? | ? | 8.4 |
| Risperidone | Risperdal Consta | Atypical | Microspheres | 12.5–75 mg/2 weeks | 21 days | ? | 3–6 days | – |
| Zuclopentixol acetate | Clopixol Acuphase | Typical | Viscoleo$^b$ | 50–200 mg/1–3 days | 1–2 days | 1–2 days | 1–2 days | 4.7–4.9 |
| Zuclopentixol decanoate | Clopixol Depot | Typical | Viscoleo$^b$ | 50–800 mg/2–4 weeks | 4–9 days | ? | 11–21 days | 7.5–9.0 |
| Note: All by intramuscular injection. Footnotes: $^a$ = Microcrystalline or nanocrystalline aqueous suspension. $^b$ = Low-viscosity vegetable oil (specifically fractionated coconut oil with medium-chain triglycerides). $^c$ = Predicted, from PubChem and DrugBank. Sources: Main: See template. ||||||||||

## Medical uses

Pipotiazine palmitate is used to treat schizophrenia.

## 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).

## Synthesis

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.