Fluphenazine

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Fluphenazine
Fluphenazine2DACS.svg
Fluphenazine3Dan.gif
Systematic (IUPAC) name
2-[4-[3-[2-(trifluoromethyl)-10H-phenothiazin-10-yl]propyl]piperazin-1-yl]ethanol
Clinical data
Trade names Prolixin
AHFS/Drugs.com monograph
MedlinePlus a682172
Pregnancy cat. C (AU) C (US)
Legal status Prescription Only (S4) (AU) -only (CA) POM (UK) -only (US)
Routes oral, IM, decanoate
Pharmacokinetic data
Bioavailability 2.7% (Oral)
Metabolism Hepatic (via CYP2D6)[1]
Half-life 14.7 hours, 6-9 days (decanoate)[1]
Excretion Urine, faeces
Identifiers
CAS number 69-23-8 YesY
ATC code N05AB02
PubChem CID 3372
IUPHAR ligand 204
DrugBank DB00623
ChemSpider 3255 YesY
UNII S79426A41Z YesY
KEGG D07977 YesY
ChEBI CHEBI:5123 YesY
ChEMBL CHEMBL726 YesY
Chemical data
Formula C22H26F3N3OS 
Mol. mass 437.523 g/mol
 YesY (what is this?)  (verify)

Fluphenazine is a typical antipsychotic drug used for the treatment of chronic psychoses such as schizophrenia.[2][3] It is a phenothiazine with a piperidine side-chain. It works by antagonising (blocking) the dopamine D2 receptors in the brain. This also leads to some of its side effects like movement disorders (like parkinsonism and akathisia) and prolactin elevation. It is given via an intramuscular or subcutaneous depot injection (as its decanoate salt) or by mouth in the form of tablets.[1] In some countries only the depot formulations are currently available.[2][3] Compared to other antipsychotics it is less prone to causing sedation, low blood pressure or anticholinergic effects but is associated with a higher frequency of movement disorders.[1]

It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.[4]

Medical uses[edit]

Its primary uses is in the treatment of schizophrenia.[5]

Adverse effects[edit]

Further information: Typical antipsychotic

Information sources:[6][5][7]

Common adverse effects (i.e. those that have an incidence ≥1%) include
  • Hypotension
  • Orthostatic hypotension
  • Somnolence/drowsiness
  • Weight gain
  • Erectile dysfunction
  • Oligomenorrhea or amenorrhea
  • Anticholinergic effects, such as:
- Dry mouth
- Constipation
- Nasal congestion
- Blurred vision
- Diminished sweating
  • Extrapyramidal side effects, such as:
- Tremor
- Akathisia
- Muscle rigidity
- Dystonia
- Parkinsonism
  • Dizziness
  • Epithelial keratopathy
  • Eye / vision finding
  • Retinitis pigmentosa
  • Photosensitivity
Uncommon side effects (0.1%≤incidence<1%) include
  • Agitation
  • Anxiety
  • Cerebral oedema
  • Depression
  • Euphoria
  • Headache
  • Ineffective temperature regulation
  • Restlessness
  • Weakness
  • Weight loss
  • Dyspepsia
  • Lens opacities (with prolonged use)
  • Photosensitivity
  • Pruritus
  • Diarrhoea
  • Galactorrhoea
  • Ejaculatory disorder
  • QT interval prolongation
Rare (incidence<0.1%) side effects include
Unknown frequency side effects include
  • Confusion
  • Decreased gag reflex
  • Silent pneumonia (likely rare)

Chemistry[edit]

Fluphenazine (4-[3-[2-(trifluoromethyl)phenothiazin-10-yl]propyl]-1-piperazineethanol), is synthesized by any of the methods described already for the preparation of trifluoperazine and related antipsychotics.

  • G.E. Ullyot, U.S. Patent 3,058,979 (1962).
  • R.C. Merril, H.L. Yale, U.S. Patent 3,394,131 (1963).
  • Smith Kline & French Lab., GB 829246  (1960).
  • Sherico Ltd., GB 833474  (1960).
  • R.C. Merril, H.L. Yale, U.S. Patent 3,194,733 (1965).
  • Yale, Harry L.; Sowinski, Francis (1960). "4-{3-[10-(2-Trifluoromethyl)-phenothiazinyl]-propyl}-1-piperazine-ethanol1 and Related Compounds. II2". Journal of the American Chemical Society 82: 2039. doi:10.1021/ja01493a047.  edit
  • E.L. Anderson, G.B. Bellizona, P.N. Craig, G.E. Jaffe, K.P. Janewaes, C. Kaiser, B.M. Hester, E.J. Nikawitz, A. Pavloff, H.E. Reift, Ch.L. Zirkle, Arzneim.-Forsch., 12, 937 (1962).

Fluphenazine synthesis.png Alkylation of 2-trifluoromethylphenothiazine using 4-formyl-1-piperazineylpropylchloride in the presence of sodamide synthesizes 2-trifluoromethyl-10-[3-(4-formyl-1-piperazinyl)propyl]phenothiazine. Further alkaline hydrolysis removes the N-formyl group, giving 2-trifluoromethyl-10-[3-(1-piperazinyl)propyl]phenothiazine. This is alkylated by 2-bromoethanol-1 acetate, which upon further acidic hydrolysis removes the protecting acetyl group, yielding fluphenazine.

  • E.L. Anderson, G.B. Bellizona, P.N. Craig, G.E. Jaffe, K.P. Janewaes, C. Kaiser, B.M. Hester, E.J. Nikawitz, A. Pavloff, H.E. Reift, Ch.L. Zirkle, Arzneim.-Forsch., 12, 937 (1962).
  • J.W. Cusic, U.S. Patent 2,766,235 (1956).

References[edit]

  1. ^ a b c d Brayfield, A, ed. (13 December 2013). "Fluphenazine". Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press. Retrieved 14 July 2014. 
  2. ^ a b Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. pp. 237, 238. ISBN 978-0-85711-084-8.  edit
  3. ^ a b Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.  edit
  4. ^ "WHO Model List of Essential Medicines". World Health Organization. October 2013. Retrieved 22 April 2014. 
  5. ^ a b "PRODUCT INFORMATION MODECATE (Fluphenazine Decanoate Oily Injection)" (PDF). TGA eBusiness Services. Bristol-Myers Squibb Australia Pty Ltd. 1 November 2012. Retrieved 9 December 2013. 
  6. ^ "FLUPHENAZINE HYDROCHLORIDE tablet, film coated [Sandoz Inc]". DailyMed. Sandoz Inc. October 2011. Retrieved 9 December 2013. 
  7. ^ "Modecate Concentrate Injection 100mg/ml - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Sanofi. 11 January 2013. Retrieved 9 December 2013.