Trifluoperazine

Overview

Trifluoperazine, marketed under the brand name Stelazine among others, is a typical antipsychotic primarily used to treat schizophrenia. It may also be used short term in those with generalized anxiety disorder but is less preferred to benzodiazepines. It is of the phenothiazine chemical class. It was approved for medical use in the United States in 1959.[1][2] WP

Uses, dosage and effects

Schizophrenia

Trifluoperazine is an effective antipsychotic for people with schizophrenia condition. 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. There is low-quality evidence that trifluoperazine reduces the risk of relapse when compared with placebo when people are followed for 5 months. 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.[3] WP

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.[4] WP

Other

It appears to be effective for people with generalized anxiety disorder but the benefit–risk ratio was unclear as of 2005.[5] WP

It has been experimentally used as a drug to kill eukaryotic pathogens such as Balamuthia in humans.[6] WP

Risks and side effects

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%. WP⚠ Wikipedia itself has flagged this text: citation needed.

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. It is also more likely to cause somnolence and anticholinergic side effects such as red eye and xerostomia (dry mouth). All antipsychotics can cause the rare and sometimes fatal neuroleptic malignant syndrome. Trifluoperazine can lower the seizure threshold. The antimuscarinic action of trifluoperazine can cause excessive dilation of the pupils (mydriasis), which increases the chances of patients with hyperopia developing glaucoma.[7–10] WP

Contraindications

Trifluoperazine is contraindicated in CNS depression, coma, and blood dyscrasias. Trifluoperazine should be used with caution in patients suffering from renal or hepatic impairment. WP

Pharmacology

Mechanism of action

Trifluoperazine has central antiadrenergic, antidopaminergic, and minimal anticholinergic effects. It is believed to work by blockading dopamine D₁ and D₂ receptors in the mesocortical and mesolimbic pathways, relieving or minimizing such symptoms of schizophrenia as hallucinations, delusions, and disorganized thought and speech. It also has antihistaminergic properties (H₁ Kᵢ = 17.5). Like other phenothiazine derivatives, it also inhibits tubulin polymerization.[7][11–16] WP

Chemistry

Formula

C21H24F3N3S PC

CAS number

117-89-5 PC

Molar mass (g/mol)

407.5 PC

IUPAC name (computed by PubChem)

10-[3-(4-methylpiperazin-1-yl)propyl]-2-(trifluoromethyl)phenothiazine PC

SMILES

CN1CCN(CC1)CCCN2C3=CC=CC=C3SC4=C2C=C(C=C4)C(F)(F)F PC

InChIKey

ZEWQUBUPAILYHI-UHFFFAOYSA-N PC

PubChem CID

5566

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Other Trifluoperazine Hydrochloride
2. Journal / agency Howland RH. Trifluoperazine: A Sprightly Old Drug. Journal of Psychosocial Nursing and Mental Health Services. January 2016. doi:10.3928/02793695-20151223-01 · PMID 26760133
3. Journal / agency Koch K, Mansi K, Haynes E, Adams CE, Sampson S, Furtado VA. Trifluoperazine versus placebo for schizophrenia. The Cochrane Database of Systematic Reviews. January 2014. doi:10.1002/14651858.CD010226.pub2 · PMID 24414883 · PMC6718209
4. Journal / agency Tardy M, Dold M, Engel RR, Leucht S. Trifluoperazine versus low-potency first-generation antipsychotic drugs for schizophrenia. The Cochrane Database of Systematic Reviews. July 2014. doi:10.1002/14651858.CD009396.pub2 · PMID 25003310 · PMC11227318
5. Journal / agency Baldwin DS, Polkinghorn C. Evidence-based pharmacotherapy of Generalized Anxiety Disorder. The International Journal of Neuropsychopharmacology. June 2005. doi:10.1017/S1461145704004870 · PMID 15576000
6. Journal / agency Deetz TR, Sawyer MH, Billman G, Schuster FL, Visvesvara GS. Successful treatment of Balamuthia amoebic encephalitis: presentation of 2 cases. Clinical Infectious Diseases. November 2003. doi:10.1086/379020 · PMID 14583863
7. Journal / agency Marques LO, Lima MS, Soares BG. Trifluoperazine for schizophrenia. Cochrane Database of Systematic Reviews. 2004. doi:10.1002/14651858.CD003545.pub2 · PMID 14974020 · PMC7003674
8. Journal / agency Smego RA, Durack DT. The neuroleptic malignant syndrome. Archives of Internal Medicine. June 1982. doi:10.1001/archinte.142.6.1183 · PMID 6124221
9. Journal / agency Hedges D, Jeppson K, Whitehead P. Antipsychotic medication and seizures: a review. Drugs of Today. July 2003. doi:10.1358/dot.2003.39.7.799445 · PMID 12973403
10. Journal / agency Boet DJ. Toxic effects of phenothiazines on the eye. Documenta Ophthalmologica. Advances in Ophthalmology. July 1970. doi:10.1007/BF00153873 · PMID 5312274
11. Journal / agency Huerta-Bahena J, Villalobos-Molina R, García-Sáinz JA. Trifluoperazine and chlorpromazine antagonize alpha 1- but not alpha2- adrenergic effects. Molecular Pharmacology. January 1983. doi:10.1016/S0026-895X(25)14231-4 · PMID 6135146
12. Journal / agency Seeman P, Lee T, Chau-Wong M, Wong K. Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature. June 1976. doi:10.1038/261717a0 · PMID 945467
13. Journal / agency Creese I, Burt DR, Snyder SH. Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. The Journal of Neuropsychiatry and Clinical Neurosciences. 1996. doi:10.1176/jnp.8.2.223 · PMID 9081563
14. Other Ebadi MS. CRC desk reference of clinical pharmacology. 1998
15. Journal / agency Hill SJ, Young M. Antagonism of central histamine H1 receptors by antipsychotic drugs. European Journal of Pharmacology. December 1978. doi:10.1016/0014-2999(78)90297-2 · PMID 32056
16. Journal / agency Baksheeva VE, La Rocca R, Allegro D, Derviaux C, Pasquier E, Roche P, Morelli X, Devred F, Golovin AV, Tsvetkov PO. NanoDSF Screening for Anti-tubulin Agents Uncovers New Structure–Activity Insights. Journal of Medicinal Chemistry. 2025. doi:10.1021/acs.jmedchem.5c01008 · PMID 40815226 · PMC12406199

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