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
Half-life 33 hours
Excretion bile/feces
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 psychoses such as schizophrenia, manic phases of bipolar disorder, agitation, and dementia. It belongs to the piperazine class of phenothiazines. The medication may help control symptoms by blocking the reuptake of dopamine in the brain. It is not entirely known how the medication works. Dopamine may be elevated in people with schizophrenia or other psychoses. It also can be used as a calming drug in horses, though such use is illegal.

The medication was originally manufactured by Bristol-Myers Squibb. It is currently marketed under the brand name Modecate, a number of generic versions are also available. It is made by several different companies. The medication comes in oral liquid, tablets (1mg, 2.5mg, 5mg, 10mg), and injectable forms (including a short-acting and long-acting form).

Its side effect profile is similar to haloperidol, namely predominantly dopamine-blocking effects, which give rise to akathisia, parkinsonism, and tremor. Long term side effects include the potentially irreversible tardive dyskinesia and the potentially fatal neuroleptic malignant syndrome.

Medical uses[edit]

Its primary uses in medicine is in the treatment of schizophrenia.[1]

Adverse effects[edit]

Information sources:[2][1][3]

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 "PRODUCT INFORMATION MODECATE (Fluphenazine Decanoate Oily Injection)" (PDF). TGA eBusiness Services. Bristol-Myers Squibb Australia Pty Ltd. 1 November 2012. Retrieved 9 December 2013. 
  2. ^ "FLUPHENAZINE HYDROCHLORIDE tablet, film coated [Sandoz Inc]". DailyMed. Sandoz Inc. October 2011. Retrieved 9 December 2013. 
  3. ^ "Modecate Concentrate Injection 100mg/ml - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Sanofi. 11 January 2013. Retrieved 9 December 2013.