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 Y
ATC code	N05AB02
PubChem	CID 3372
IUPHAR ligand	204
DrugBank	DB00623
ChemSpider	3255 Y
UNII	S79426A41Z Y
KEGG	D07977 Y
ChEBI	CHEBI:5123 Y
ChEMBL	CHEMBL726 Y
Chemical data
Formula	C22H26F3N3OS
Mol. mass	437.523 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/C22H26F3N3OS/c23-22(24,25)17-6-7-21-19(16-17)28(18-4-1-2-5-20(18)30-21)9-3-8-26-10-12-27(13-11-26)14-15-29/h1-2,4-7,16,29H,3,8-15H2 Y Key:PLDUPXSUYLZYBN-UHFFFAOYSA-N Y
Y (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.

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

Further information: Typical antipsychotic

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. 
• 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).

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

• "Fluphenazine". Davis's Drug Guide for Nurses, Eighth Edition. F.A. Davis Company, 2005. ISBN 0-8036-2455-7.
• FLUPHENAZINE DICHLORHYDRATE [Article in French] Biam Last Updated: 11 December 2000. Accessed 14 September 2005.