Chemistry:Pipotiazine

Short description: Typical antipsychotic medication

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) 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
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

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:

Pipotiazine palmitate compared to oral antipsychotics for 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

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

Patents: Sino:

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.