Pipotiazine

Pipotiazine (Piportil), also known as pipothiazine, is a typical antipsychotic of the phenothiazine class^[2] used in the United Kingdom and other countries for the treatment of schizophrenia.^[3] Its properties are similar to those of chlorpromazine. A 2004 systematic review investigated its efficacy for people with schizophrenia:

Pipotiazine palmitate compared to oral antipsychotics for schizophrenia^[4]

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.[4]
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

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Pharmacokinetics of long-acting injectable antipsychotics

Medication	Brand name	Class	Vehicle	Dosage	Tmax	t1/2 single	t1/2 multiple	logPc	Ref
Aripiprazole lauroxil	Aristada	Atypical	Watera	441–1064 mg/4–8 weeks	24–35 days	?	54–57 days	7.9–10.0
Aripiprazole monohydrate	Abilify Maintena	Atypical	Watera	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	[5]
Clopentixol decanoate	Sordinol Depot	Typical	Viscoleob	50–600 mg/1–4 weeks	4–7 days	?	19 days	9.0	[6]
Flupentixol decanoate	Depixol	Typical	Viscoleob	10–200 mg/2–4 weeks	4–10 days	8 days	17 days	7.2–9.2	[6][7]
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	[8][9][10]
Fluphenazine enanthate	Prolixin Enanthate	Typical	Sesame oil	12.5–100 mg/1–4 weeks	2–3 days	4 days	?	6.4–7.4	[9]
Fluspirilene	Imap, Redeptin	Typical	Watera	2–12 mg/1 week	1–8 days	7 days	?	5.2–5.8	[11]
Haloperidol decanoate	Haldol Decanoate	Typical	Sesame oil	20–400 mg/2–4 weeks	3–9 days	18–21 days		7.2–7.9	[12][13]
Olanzapine pamoate	Zyprexa Relprevv	Atypical	Watera	150–405 mg/2–4 weeks	7 days	?	30 days	–
Oxyprothepin decanoate	Meclopin	Typical	?	?	?	?	?	8.5–8.7
Paliperidone palmitate	Invega Sustenna	Atypical	Watera	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	[14]
Pipotiazine palmitate	Piportil Longum	Typical	Viscoleob	25–400 mg/4 weeks	9–10 days	?	14–21 days	8.5–11.6	[7]
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	Viscoleob	50–200 mg/1–3 days	1–2 days	1–2 days		4.7–4.9
Zuclopentixol decanoate	Clopixol Depot	Typical	Viscoleob	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.

Pipotiazine

Clinical data
Trade names	Piportil
AHFS/Drugs.com	International Drug Names
Routes of administration	Oral, IM
ATC code	N05AC04 (WHO)
Legal status
Legal status	BR: Class C1 (Other controlled substances)[1] In general: ℞ (Prescription only)
Identifiers
IUPAC name 10-[3-[4-(2-hydroxyethyl)-1-piperidyl]propyl]-N,N-dimethyl-phenothiazine-2-sulfonamide
CAS Number	39860-99-6
PubChem CID	62867
IUPHAR/BPS	7557
DrugBank	DB01621
ChemSpider	56598
UNII	L903J9JPYV
KEGG	D08385
ChEMBL	ChEMBL398880
CompTox Dashboard (EPA)	DTXSID40192913
ECHA InfoCard	100.049.672
Chemical and physical data
Formula	C24H33N3O3S2
Molar mass	475.67 g·mol−1
3D model (JSmol)	Interactive image
SMILES CN(C)S(=O)(=O)C1=CC2=C(C=C1)SC3=CC=CC=C3N2CCCN4CCC(CC4)CCO

Medical uses

Pipotiazine palmitate is used to treat schizophrenia.^[15]

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).^[15]

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).^[16]

Synthesis

Patents:^[17][18] Sino:^[19]

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.^[20]