Trifluoperazine

Trifluoperazine
Clinical data
Trade namesStelazine, Eskazinyl, Eskazine, Jatroneural, others
AHFS/Drugs.comMonograph
MedlinePlusa682121
Pregnancy
category
  • AU: C
Routes of
administration		By mouth, IM
Drug classTypical antipsychotic
ATC code
Legal status
Legal status
Pharmacokinetic data
MetabolismLiver
Elimination half-life10–20 hours
Identifiers
  • 10-[3-(4-methylpiperazin-1-yl)propyl]-
    2-(trifluoromethyl)-10H-phenothiazine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.003.837 Edit this at Wikidata
Chemical and physical data
FormulaC21H24F3N3S
Molar mass407.50 g·mol−1
3D model (JSmol)
  • FC(F)(F)c2cc1N(c3c(Sc1cc2)cccc3)CCCN4CCN(C)CC4
  • InChI=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 checkY
  • Key:ZEWQUBUPAILYHI-UHFFFAOYSA-N checkY
  (verify)

Trifluoperazine, marketed under the brand name Stelazine among others, is a typical antipsychotic primarily used to treat schizophrenia.[3] It may also be used short term in those with generalized anxiety disorder but is less preferred to benzodiazepines.[3] It is of the phenothiazine chemical class. It was approved for medical use in the United States in 1959.[4]

Medical uses

Schizophrenia

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

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.[6]

Other

It appears to be effective for people with generalized anxiety disorder but the benefit–risk ratio was unclear as of 2005.[7]

It has been experimentally used as a drug to kill eukaryotic pathogens in humans.[8]

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]

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.[9] It is also more likely to cause somnolence and anticholinergic side effects such as red eye and xerostomia (dry mouth).[9] All antipsychotics can cause the rare and sometimes fatal neuroleptic malignant syndrome.[10] Trifluoperazine can lower the seizure threshold.[11] The antimuscarinic action of trifluoperazine can cause excessive dilation of the pupils (mydriasis), which increases the chances of patients with hyperopia developing glaucoma.[12]

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.

Mechanism of action

Trifluoperazine has central antiadrenergic,[13] antidopaminergic,[14][15] and minimal anticholinergic effects.[16] 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.[9] It also has antihistaminergic properties (H1 Ki = 17.5[17]).

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 mg of tranylcypromine and 1 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

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  2. ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  3. ^ a b "Trifluoperazine Hydrochloride". The American Society of Health-System Pharmacists. Retrieved 8 January 2017.
  4. ^ Howland RH (January 2016). "Trifluoperazine: A Sprightly Old Drug". Journal of Psychosocial Nursing and Mental Health Services. 54 (1): 20–2. doi:10.3928/02793695-20151223-01. PMID 26760133.
  5. ^ a b c d Koch K, Mansi K, Haynes E, Adams CE, Sampson S, Furtado VA (January 2014). "Trifluoperazine versus placebo for schizophrenia". The Cochrane Database of Systematic Reviews. 1 (1): CD010226. doi:10.1002/14651858.CD010226.pub2. PMC 6718209. PMID 24414883. Wikiversity:Trifluoperazine versus placebo for schizophrenia § References
  6. ^ Tardy M, Dold M, Engel RR, Leucht S (July 2014). "Trifluoperazine versus low-potency first-generation antipsychotic drugs for schizophrenia". The Cochrane Database of Systematic Reviews (7): CD009396. doi:10.1002/14651858.CD009396.pub2. PMC 11227318. PMID 25003310.
  7. ^ Baldwin DS, Polkinghorn C (June 2005). "Evidence-based pharmacotherapy of Generalized Anxiety Disorder". The International Journal of Neuropsychopharmacology. 8 (2): 293–302. doi:10.1017/S1461145704004870. PMID 15576000.
  8. ^ Deetz TR, Sawyer MH, Billman G, Schuster FL, Visvesvara GS (November 2003). "Successful treatment of Balamuthia amoebic encephalitis: presentation of 2 cases". Clinical Infectious Diseases. 37 (10): 1304–1312. doi:10.1086/379020. PMID 14583863.
  9. ^ a b c Marques LO, Lima MS, Soares BG (2004). "Trifluoperazine for schizophrenia". Cochrane Database of Systematic Reviews. 2004 (1): CD003545. doi:10.1002/14651858.CD003545.pub2. PMC 7003674. PMID 14974020.
  10. ^ Smego RA, Durack DT (June 1982). "The neuroleptic malignant syndrome". Archives of Internal Medicine. 142 (6): 1183–5. doi:10.1001/archinte.142.6.1183. PMID 6124221.
  11. ^ Hedges D, Jeppson K, Whitehead P (July 2003). "Antipsychotic medication and seizures: a review". Drugs of Today. 39 (7): 551–7. doi:10.1358/dot.2003.39.7.799445. PMID 12973403.
  12. ^ Boet DJ (July 1970). "Toxic effects of phenothiazines on the eye". Documenta Ophthalmologica. Advances in Ophthalmology. 28 (1): 1–69. doi:10.1007/BF00153873. hdl:1765/26543. PMID 5312274. S2CID 26145461.
  13. ^ Huerta-Bahena J, Villalobos-Molina R, García-Sáinz JA (January 1983). "Trifluoperazine and chlorpromazine antagonize alpha 1- but not alpha2- adrenergic effects". Molecular Pharmacology. 23 (1): 67–70. PMID 6135146. Retrieved 2009-06-21.
  14. ^ Seeman P, Lee T, Chau-Wong M, Wong K (June 1976). "Antipsychotic drug doses and neuroleptic/dopamine receptors". Nature. 261 (5562): 717–9. Bibcode:1976Natur.261..717S. doi:10.1038/261717a0. PMID 945467. S2CID 4164538.
  15. ^ Creese I, Burt DR, Snyder SH (1996). "Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs". The Journal of Neuropsychiatry and Clinical Neurosciences. 8 (2): 223–6. doi:10.1176/jnp.8.2.223. PMID 9081563. Archived from the original on 2011-07-27. Retrieved 2009-06-21.
  16. ^ Ebadi MS (1998). "Trifluoperazine Hydrochloride". CRC desk reference of clinical pharmacology (illustrated ed.). CRC Press. ISBN 978-0-8493-9683-0. Retrieved 2009-06-21.
  17. ^ Hill SJ, Young M (December 1978). "Antagonism of central histamine H1 receptors by antipsychotic drugs". European Journal of Pharmacology. 52 (3–4): 397–399. doi:10.1016/0014-2999(78)90297-2. PMID 32056.