Fluphenazine

Fluphenazine
Systematic (IUPAC) name
2-[4-[3-[2-(trifluoromethyl)-10H-phenothiazin-10-yl]propyl]piperazin-1-yl]ethanol
Clinical data
AHFS/Drugs.com monograph
MedlinePlus a682172
Pregnancy cat. C(US)
Legal status Prescription only
Routes oral, IM, decanoate
Pharmacokinetic data
Bioavailability 40% - 50%
Metabolism Hepatic
Half-life 15 to 30 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
SMILES eMolecules & PubChem
 YesY(what is this?)  (verify)

Fluphenazine is a typical antipsychotic drug used for the treatment of psychoses such as schizophrenia and acute manic phases of bipolar disorder. It belongs to the piperazine class of phenothiazines.

Its main use is as a long acting injection given once every two or three weeks to people with schizophrenia who suffer frequent relapses of illness. 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.

Contents

Brand names

Fluphenazine decanoate: Modecate, Prolixin Decanoate, Dapotum D, Anatensol, Fludecate, Sinqualone Deconoate
Fluphenazine enanthate: Dapotum Injektion, Flunanthate, Moditen Enanthate Injection, Sinqualone Enanthate
Fluphenazine hydrochloride: Prolixin, Permitil, Dapotum, Lyogen, Moditen, Omca, Sediten, Selecten, Sevinol, Sinqualone, Trancin

flucate

Pharmacokinetics

Fluphenazine has an incomplete oral bioavailability of 40% to 50% (due to extensive first pass metabolization in the liver). Its half life is 15 to 30 hours.

Dosing

12.5 mg of fluphenazine decanoate is roughly equivalent to 100 mg of zuclopenthixol decanoate or 20 mg of flupentixol decanoate.

Side effects

Notable side effects include akathisia, extrapyramidal side effects, including tardive dyskinesia and Rabbit syndrome. The frequency and severity of extrapyramidal side effects are direct proportional to the dose given and the duration of treatment. Mostly notably, although rare, it can cause hypothermia because it inhibits ability to shiver.

Sedative, allergic-toxic and anticholinergic/sympatholytic side effects are less likely to occur compared with chlorpromazine. The direct deposition of fluphenazine in the cornea and retina has so far not been reported.

Neuroleptic malignant syndrome, although rare, is a potentially lethal side effect of all antipsychotics.

Chemistry

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