Editing Trifluoperazine

{{Short description|Typical antipsychotic medication}}
{{drugbox
| verifiedrevid = 470614430
| IUPAC_name = 10-[3-(4-methylpiperazin-1-yl)propyl]-<br/>2-(trifluoromethyl)-10''H''-phenothiazine
| image = Trifluoperazine.svg
| image_class = skin-invert-image
| width = 250

<!--Clinical data-->
| Drugs.com = {{drugs.com|monograph|trifluoperazine-hydrochloride}}
| MedlinePlus = a682121
| pregnancy_AU = C
| pregnancy_US = C
| legal_BR = C1
| legal_BR_comment = <ref>{{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}}</ref>
| legal_UK = POM
| legal_US = Rx-only
| routes_of_administration = By mouth, [[Intramuscular injection|IM]]
| class = [[Typical antipsychotic]]

<!--Pharmacokinetic data-->
| bioavailability = 
| metabolism = [[Liver]]
| elimination_half-life = 10–20 hours
| excretion =

<!--Identifiers-->
| tradename = Stelazine, Eskazinyl, Eskazine, Jatroneural, others
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 117-89-5
| ATC_prefix = N05
| ATC_suffix = AB06
| PubChem = 5566
| IUPHAR_ligand = 214
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00831
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 5365
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 214IZI85K3
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 45951
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 422
| PDB_ligand = TFP

<!--Chemical data-->
| C=21 | H=24 | F=3 | N=3 | S=1
| smiles = FC(F)(F)c2cc1N(c3c(Sc1cc2)cccc3)CCCN4CCN(C)CC4
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C21H24F3N3S/c1-25-11-13-26(14-12-25)9-4-10-27-17-5-2-3-6-19(17)28-20-8-7-16(15-18(20)27)21(22,23)24/h2-3,5-8,15H,4,9-14H2,1H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = ZEWQUBUPAILYHI-UHFFFAOYSA-N
|drug_name=|alt=|caption=|type=|legal_status=|licence_EU=|pregnancy_category=|licence_US=}}

'''Trifluoperazine''', marketed under the brand name '''Stelazine''' among others, is a [[typical antipsychotic]] primarily used to treat [[schizophrenia]].<ref name=AHFS2017>{{cite web|title=Trifluoperazine Hydrochloride|url=https://www.drugs.com/monograph/trifluoperazine-hydrochloride.html|publisher=The American Society of Health-System Pharmacists|access-date= 8 January 2017}}</ref> It may also be used short term in those with [[generalized anxiety disorder]] but is less preferred to [[benzodiazepines]].<ref name=AHFS2017/> It is of the [[phenothiazine]] [[chemical class]].  It was approved for medical use in the United States in 1959.<ref name="Howland2016">{{cite journal |vauthors=Howland RH |title=Trifluoperazine: A Sprightly Old Drug |journal=[[Journal of Psychosocial Nursing and Mental Health Services]] |volume=54 |issue=1 |pages=20–2 |date=January 2016 |pmid=26760133 |doi=10.3928/02793695-20151223-01}}</ref>

== Medical uses ==
===Schizophrenia===
Trifluoperazine is an effective [[antipsychotic]] for people with schizophrenia condition.<ref name=Koc2014/> There is low-quality evidence that trifluoperazine increases the chance of being improved when compared to placebo when people are followed up for 19 weeks.<ref name=Koc2014/> There is low-quality evidence that trifluoperazine reduces the risk of relapse when compared with placebo when people are followed for 5 months.<ref name=Koc2014/> As of 2014 there was no good evidence for a difference between trifluoperazine and [[placebo]] with respect to the risk of experiencing intensified symptoms over a 16-week period nor in reducing significant agitation or distress.<ref name=Koc2014>{{cite journal | vauthors = Koch K, Mansi K, Haynes E, Adams CE, Sampson S, Furtado VA | title = Trifluoperazine versus placebo for schizophrenia | journal = The Cochrane Database of Systematic Reviews | volume = 1 | issue = 1 | pages = CD010226 | date = January 2014 | pmid = 24414883 | pmc = 6718209 | doi = 10.1002/14651858.CD010226.pub2 }} {{slink|Wikiversity:Trifluoperazine_versus_placebo_for_schizophrenia|References}}</ref>

There is no good evidence that trifluoperazine is more effective for schizophrenia than lower-potency antipsychotics like [[chlorpromazine]], [[chlorprothixene]], [[thioridazine]] and [[levomepromazine]], but trifluoperazine appears to cause more adverse effects than these drugs.<ref>{{cite journal | vauthors = Tardy M, Dold M, Engel RR, Leucht S | title = Trifluoperazine versus low-potency first-generation antipsychotic drugs for schizophrenia | journal = The Cochrane Database of Systematic Reviews | issue = 7 | pages = CD009396 | date = July 2014 | pmid = 25003310 | doi = 10.1002/14651858.CD009396.pub2 | pmc = 11227318 }}</ref>

===Other===
It appears to be effective for people with [[generalized anxiety disorder]] but the benefit{{endash}}risk ratio was unclear as of 2005.<ref>{{cite journal | vauthors = Baldwin DS, Polkinghorn C | title = Evidence-based pharmacotherapy of Generalized Anxiety Disorder | journal = The International Journal of Neuropsychopharmacology | volume = 8 | issue = 2 | pages = 293–302 | date = June 2005 | pmid = 15576000 | doi = 10.1017/S1461145704004870 | doi-access = free }}</ref>

It has been experimentally used as a drug to kill [[eukaryotic]] [[pathogens]] such as ''[[Balamuthia]]'' in humans.<ref name="DeetzSawyer2003">{{cite journal | vauthors = Deetz TR, Sawyer MH, Billman G, Schuster FL, Visvesvara GS | title = Successful treatment of Balamuthia amoebic encephalitis: presentation of 2 cases | journal = Clinical Infectious Diseases | volume = 37 | issue = 10 | pages = 1304–1312 | date = November 2003 | pmid = 14583863 | doi = 10.1086/379020 | doi-access = free }}</ref>

== Side effects ==
Its use in  many parts of the world has declined because of highly frequent and severe early and late [[tardive dyskinesia]], a type of  [[extrapyramidal symptom]].  The annual development rate of tardive dyskinesia may be as high as 4%.{{Citation needed|date=April 2009}}

A 2004 [[meta-analysis]] of the studies on trifluoperazine found that it is more likely than placebo to cause extrapyramidal side effects such as [[akathisia]], [[dystonia]], and [[Parkinsonism]].<ref name="Marq">{{cite journal |vauthors=Marques LO, Lima MS, Soares BG | title = Trifluoperazine for schizophrenia| journal = Cochrane Database of Systematic Reviews| issue = 1| pages = CD003545| year = 2004| volume = 2004| pmid = 14974020| doi = 10.1002/14651858.CD003545.pub2| pmc = 7003674}}</ref> It is also more likely to cause [[somnolence]] and anticholinergic side effects such as [[Red eye (medicine)|red eye]] and [[xerostomia]] (dry mouth).<ref name="Marq"/> All antipsychotics can cause the rare and sometimes fatal [[neuroleptic malignant syndrome]].<ref>{{cite journal|vauthors=Smego RA, Durack DT | title = The neuroleptic malignant syndrome| journal = Archives of Internal Medicine| volume = 142| issue = 6| pages = 1183–5| date=June 1982| pmid = 6124221| doi = 10.1001/archinte.142.6.1183}}</ref> Trifluoperazine can lower the seizure threshold.<ref>{{cite journal|vauthors=Hedges D, Jeppson K, Whitehead P | title = Antipsychotic medication and seizures: a review| journal = Drugs of Today| volume = 39| issue = 7| pages = 551–7| date=July 2003| pmid = 12973403| doi = 10.1358/dot.2003.39.7.799445}}</ref> The [[antimuscarinic]] action of trifluoperazine can cause excessive dilation of the pupils ([[mydriasis]]), which increases the chances of patients with [[hyperopia]] developing [[glaucoma]].<ref>{{cite journal | vauthors = Boet DJ | title = Toxic effects of phenothiazines on the eye | journal = Documenta Ophthalmologica. Advances in Ophthalmology | volume = 28 | issue = 1 | pages = 1–69 | date = July 1970 | pmid = 5312274 | doi = 10.1007/BF00153873 | hdl-access = free | s2cid = 26145461 | hdl = 1765/26543 }}</ref>

== Contraindications ==
Trifluoperazine is contraindicated in [[CNS depression]], [[coma]], and [[blood dyscrasia]]s. Trifluoperazine should be used with caution in patients suffering from renal or hepatic impairment.

== Mechanism of action==
Trifluoperazine has central [[antiadrenergic]],<ref>{{cite journal|vauthors=Huerta-Bahena J, Villalobos-Molina R, García-Sáinz JA | title = Trifluoperazine and chlorpromazine antagonize alpha 1- but not alpha2- adrenergic effects| journal = Molecular Pharmacology| volume = 23| issue = 1| pages = 67–70| date=January 1983| pmid = 6135146| url = http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=6135146| access-date = 2009-06-21}}</ref> [[antidopaminergic]],<ref>{{cite journal|vauthors=Seeman P, Lee T, Chau-Wong M, Wong K | title = Antipsychotic drug doses and neuroleptic/dopamine receptors| journal = Nature| volume = 261| issue = 5562| pages = 717–9| date=June 1976| pmid = 945467| doi = 10.1038/261717a0| bibcode=1976Natur.261..717S| s2cid = 4164538}}</ref><ref>{{cite journal| vauthors = Creese I, Burt DR, Snyder SH| title = Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs| journal = The Journal of Neuropsychiatry and Clinical Neurosciences| volume = 8| issue = 2| pages = 223–6| year = 1996| pmid = 9081563| doi = 10.1176/jnp.8.2.223| url = http://neuro.psychiatryonline.org/cgi/content/abstract/8/2/223| access-date = 2009-06-21| archive-date = 2011-07-27| archive-url = https://archive.today/20110727191024/http://neuro.psychiatryonline.org/cgi/content/abstract/8/2/223| url-status = dead}}</ref> and minimal [[anticholinergic]] effects.<ref>{{cite book| vauthors = Ebadi MS | title=CRC desk reference of clinical pharmacology| url=https://books.google.com/books?id=-EAxShTKfGAC| access-date=2009-06-21| edition=illustrated| year=1998| publisher=CRC Press| isbn=978-0-8493-9683-0| chapter=Trifluoperazine Hydrochloride| chapter-url=https://books.google.com/books?id=-EAxShTKfGAC&q=trifluoperazine%20anticholinergic&pg=PA580}}</ref> It is believed to work by blockading dopamine [[Dopamine receptor D1|D<sub>1</sub>]] and [[Dopamine receptor D2|D<sub>2</sub>]] receptors in the [[Mesocortical pathway|mesocortical]] and [[mesolimbic pathway]]s, relieving or minimizing such symptoms of schizophrenia as [[hallucination]]s, [[delusion]]s, and disorganized thought and speech.<ref name="Marq"/> It also has antihistaminergic properties ([[Histamine H1 receptor|H<sub>1</sub>]] [[Binding constant|K<sub>i</sub>]] = 17.5<ref>{{cite journal | vauthors = Hill SJ, Young M | title = Antagonism of central histamine H1 receptors by antipsychotic drugs | journal = European Journal of Pharmacology | volume = 52 | issue = 3–4 | pages = 397–399 | date = December 1978 | pmid = 32056 | doi = 10.1016/0014-2999(78)90297-2 }}</ref>).

== Names ==
Brand names include Eskazinyl, Eskazine, Jatroneural, Modalina, Sizonil, Stelazine, Stilizan, Terfluzine, Trifluoperaz and Triftazin.

In the [[United Kingdom]] and some other countries, trifluoperazine is sold and marketed under the brand 'Stelazine'.

The drug is sold as tablet, liquid and 'Trifluoperazine-injectable USP' for deep [[intramuscular]] short-term use.

In the past, trifluoperazine was used in fixed combinations with the [[MAO inhibitor]] (antidepressant) [[tranylcypromine]] ([[tranylcypromine/trifluoperazine]]) to attenuate the strong stimulating effects of this antidepressant. This combination was sold under the brand name Jatrosom N, Stelapar, Parstelin, among others. It remained available in [[Italy]] under the brand name Parmodalin (10&nbsp;mg of tranylcypromine and 1&nbsp;mg of trifluoperazine) until its discontinuation in 2019.

Likewise, a combination with [[amobarbital]] (potent sedative/hypnotic agent) for the amelioration of [[psychoneurosis]] and [[insomnia]] existed under the brand name Jalonac.

==References==
{{Reflist|30em}}

{{Antipsychotics}}
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[[Category:Trifluoromethyl compounds]]
[[Category:Phenothiazines]]
[[Category:4-Methylpiperazin-1-yl compounds]]
[[Category:Typical antipsychotics]]