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 (S4) (AU) ℞ 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 FC(F)(F)c2cc1N(c3c(Sc1cc2)cccc3)CCCN4CCN(CCO)CC4
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, manic phases of bipolar disorder, agitation, and dementia. It belongs to the piperazine class of phenothiazines. The medication may help control symptoms by blocking or lessening the effects of dopamine in the brain. It is not entirely known how the medication works. However, it is known to block or lessen the effects of dopamine, a chemical in the brain. 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. Although brand-name fluphenazine is no longer manufactured, a generic version is still 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.

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

In children over age 16 and in adults, fluphenazine is usually given in oral dosages ranging from 0.5–10 mg daily. The total dosage is usually divided and taken two to four times throughout the day. The dosage is typically reduced at a gradual pace over time to a range between 1 mg and 5 mg. Older adults usually receive lower doses that begin in the range of 1 mg–2.5 mg per day. In children under age 16, the usual range is 0.25–3.5 mg per day divided into several doses. Maximum dosage is normally 10 mg per day for this age group.

This drug is also available by injection. In adults, slow-acting injections into the muscle range from 1.25–10 mg per day divided into several doses. A long-acting injectable form can also be administered to patients who have been stabilized on the drug every month. The dose for the long-acting preparation ranges from 12.5–25 mg given every one to four weeks in adults. The dosage for children is lower in all cases.

Side effects

Further information: Typical antipsychotic

Notable side effects include akathisia, extrapyramidal side effects, including tardive dyskinesia and Rabbit syndrome. Fluphenazine use may lead to the development of symptoms that resemble Parkinson's disease. These symptoms may include a tight or mask-like expression on the face, drooling, tremors, pill-rolling motions in the hands, cogwheel rigidity (abnormal rigidity in muscles characterized by jerky movements when the muscle is passively stretched), and a shuffling gait. Taking anti-Parkinson drugs benztropine mesylate or trihexyphenidyl hydrochloride along with the fluphenazine usually controls these symptoms.

Fluphenazine also has the potential to produce a serious, incurable side effect called tardive dyskinesia . This syndrome consists of involuntary twitches of eyes and body parts which may appear years after taking the drug, and no do not usually disappear even after stopping taking fluphenazine. People with tardive dyskinesia cannot control their reflexual movements of tongue, jaw, mouth, or other muscle groups. Consumers of fluphenazine may increase their risk of developing tardive dyskinesia by the length of time they stay on it, the higher the dosage, and the older they are. Women are also more sensitive to developing tardive dyskinesia at lower dosages. There is no known cure or effective treatment to stop tardive dyskinesia.

The frequency and severity of 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 the 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.

Fluphenazine - http://www.minddisorders.com/Flu-Inv/Fluphenazine.html#b#ixzz28etEdxu8 - dose, children, effects, therapy, adults, withdrawal, drug, person