Periciazine

Periciazine (INN), also known as pericyazine (BAN) or propericiazine, is a drug that belongs to the phenothiazine class of typical antipsychotics.

Periciazine

Clinical data
Pregnancy category	AU: C
Routes of administration	Oral
Drug class	Typical antipsychotic
ATC code	N05AC01 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) BR: Class C1 (Other controlled substances)[1] CA: ℞-only UK: POM (Prescription only) In general: ℞ (Prescription only)
Pharmacokinetic data
Metabolism	Hepatic (mostly via conjugation)[2]
Elimination half-life	12 h[2]
Excretion	Renal[2]
Identifiers
IUPAC name 10-[3-(4-hydroxypiperidin-1-yl)propyl]-10H-phenothiazine-2-carbonitrile
CAS Number	2622-26-6 Y
PubChem CID	4747
DrugBank	DB01608 N
ChemSpider	4585 N
UNII	3405M6FD73
KEGG	D01485 Y
ChEBI	CHEBI:31981 N
ChEMBL	ChEMBL251940 N
CompTox Dashboard (EPA)	DTXSID5045910
ECHA InfoCard	100.018.248
Chemical and physical data
Formula	C21H23N3OS
Molar mass	365.50 g·mol−1
3D model (JSmol)	Interactive image
SMILES C1CN(CCC1O)CCCN2C3=CC=CC=C3SC4=C2C=C(C=C4)C#N
InChI InChI=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 N Key:LUALIOATIOESLM-UHFFFAOYSA-N N
NY (what is this?)  (verify)

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.^[3]

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 disorders such as schizophrenia. There is insufficient evidence to determine whether periciazine is more or less effective than other antipsychotics.^[2] A 2014 systematic review compared periciazine with typical antipsychotics for schizophrenia:

Periciazine versus typical antipsychotic for schizophrenia^[4]

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 side effects than other antipsychotics.[4]
Outcome Findings in words Findings in numbers Quality of evidence Global state Not improved 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. RR 1.24 (0.93 to 1.66) Very low Adverse events Extrapyramidal side effect 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. RR 0.59 (0.38 to 0.89) Very low Leaving the study early For any reasons 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. RR 0.46 (0.11 to 1.9) Very low 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.^[5]

Adverse effects

Periciazine is a rather sedating and anticholinergic antipsychotic, and despite being classed with the typical antipsychotics, its risk of extrapyramidal side effects is comparatively low.^[6] It has a relatively high risk of causing hyperprolactinaemia and a moderate risk of causing weight gain and orthostatic hypotension.^[6]

Synthesis

Thieme Patent (Ex V):^[7]

The final step in the synthesis involves the alkylation of 3-(2-cyanophenothiazin-10-yl)propyl 4-methylbenzenesulfonate, CID:134990672 (1) with 4-Piperidinol [5382-16-1] (2) giving Periciazine (3).