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tranquilizer used to treat psychotic disorders

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/11/07 14:02:21」(JST)

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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. 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. Itis 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.

Brand names[edit]

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[edit]

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[edit]

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[edit]

Further information: Typical antipsychotic

Information sources:^[2]^[3]^[4]^[5]

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

Blood dyscrasia (e.g. neutropaenia, agranulocytosis, leukopaenia, etc.)
Seizures
Paralytic ileus
Torsades de Pointes
Heatstroke
Hypothermia
Priapism
Drug-induced Systemic lupus erythematosus
Obstipation
Neuroleptic malignant syndrome'
Tardive dyskinesia
Cholestatic jaundice syndrome

Unknown frequency side effects include

Confusion
Decreased gag reflux
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).

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]

^ ^a ^b ^c Truven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Sep 29]. Greenwood Village, CO: Thomsen Healthcare; 2013.
^ Truven Health Analytics, Inc. DrugPoint® System (Internet) [cited 2013 Sep 29]. Greenwood Village, CO: Thomsen Healthcare; 2013.
^ PRODUCT INFORMATION MODECATE (Fluphenazine Decanoate Oily Injection) [Internet]. 2012 [cited 2013 Sep 29]. Available from: https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-02643-3
^ fluphenazine (Rx) - Modecate, Modecate Concentrate, Moditen, Prolixin, RhoFluphenazine [Internet]. Medscape Reference. [cited 2013 Sep 29]. Available from: http://reference.medscape.com/drug/fluphenazine-342973#4
^ Joint Formulary Committee. British National Formulary (BNF) 65. Pharmaceutical Pr; 2013.

"Fluphenazine". Davis's Drug Guide for Nurses, Eighth Edition. F.A. Davis Company, 2005. ISBN 0-8036-2455-7.
Fluphenazine - http://www.minddisorders.com/Flu-Inv/Fluphenazine.html#b#ixzz28etEdxu8 - dose, children, effects, therapy, adults, withdrawal, drug, person

UpToDate Contents

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1. 統合失調症に対する薬物療法：持効性抗精神病薬注射製剤 pharmacotherapy for schizophrenia long acting injectable antipsychotic drugs
2. 第1世代抗精神病剤：薬理学、投与、および副作用の比較 first generation antipsychotic medications pharmacology administration and comparative side effects
3. 統合失調症に対する薬物療法：急性期および維持期の治療 pharmacotherapy for schizophrenia acute and maintenance phase treatment
4. 出産後女性における双極性障害：治療 bipolar disorder in postpartum women treatment
5. 妊婦女性における双極性障害：躁病、軽躁、混合エピソードの治療 bipolar disorder in pregnant women treatment of mania hypomania and mixed episodes

English Journal

Long-acting neuroleptic use for reproductive management of non-domestic ungulates using the domestic goat (Capra hircus) as a model.

Weiss RB1, Schook MW, Wolfe BA.Author information 1The Wilds, Cumberland, Ohio.AbstractFluphenazine decanoate is a long-acting phenothiazine neuroleptic that attenuates the stress response and may be useful during intensive handling for reproductive procedures in non-domestic ungulates. However, phenothiazines are also associated with elevated serum prolactin, which can suppress fertility in some species. For this study, 10 female domestic goats were used as a model for non-domestic caprids to test effects of fluphenazine decanoate on serum cortisol and reproductive cyclicity following estrus synchronization. Two identical trials were conducted during the breeding season, employing a random crossover design. First, females underwent estrus synchronization using a 14-day treatment with progesterone (330 mg; CIDR). After 7 days of CIDR exposure, the treatment group (n = 5) received fluphenazine decanoate (1.0 mg/kg IM) and controls (n = 5) received an equivalent volume of 0.9% saline IM. At CIDR withdrawal (Day 14), animals received 125 mg cloprostenol sodium to lyse any luteal tissue and synchronize estrus. Blood was collected every 2 hr from 36 hr after CIDR withdrawal until 24 hr after standing estrus, or up to 5 days to monitor stress and reproductive hormones. Serum cortisol, prolactin, luteinizing hormone (LH) and progesterone concentrations were determined by enzyme immunoassay. While treatment with fluphenazine was associated with lower cortisol concentrations compared to controls (P = 0.001), 4 of the 10 treated animals experienced elevated serum prolactin, suppression of the LH surge and inhibition of ovulation. These findings suggest that long-acting neuroleptic drugs reduce the adrenal stress response, but may interfere with reproductive responses and negatively influence breeding success. Zoo Biol. XX:XX-XX, 2014. © 2014 Wiley Periodicals, Inc.
Zoo biology.Zoo Biol.2014 Mar 18. doi: 10.1002/zoo.21125. [Epub ahead of print]
Fluphenazine decanoate is a long-acting phenothiazine neuroleptic that attenuates the stress response and may be useful during intensive handling for reproductive procedures in non-domestic ungulates. However, phenothiazines are also associated with elevated serum prolactin, which can suppress ferti
PMID 24644127

Va'a fakalelei 'atamai: restoring the mind in the Kingdom of Tonga.

Nielssen O1, Fukui A, Fawkner L, Walker K.Author information 1Psychiatrist, Level 8 Practice, Sydney, NSW, and St Vincents Hospital.AbstractOBJECTIVE: We aim to report on the practice of psychiatry in the Kingdom of Tonga.
Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists.Australas Psychiatry.2014 Feb 10. [Epub ahead of print]
OBJECTIVE: We aim to report on the practice of psychiatry in the Kingdom of Tonga.METHOD: We provide a description of the findings from a visit to Vaiola Hospital and data provided by the chief psychiatrist of Tonga.RESULTS: The practice of psychiatry in Tonga reflects the difficulties of providing
PMID 24516194

Effectiveness of saikokaryukotsuboreito (herbal medicine) for antipsychotic-induced sexual dysfunction in male patients with schizophrenia: a description of two cases.

Takashi T1, Uchida H2, Suzuki T3, Mimura M1.Author information 1Department of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.2Department of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan ; Geriatric Mental Health Program, Centre for Addiction and Mental Health, Toronto, ON, Canada M5T 1R8.3Department of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan ; Department of Psychiatry, Inokashira Hospital, Tokyo 181-0012, Japan.AbstractAntipsychotics sometimes cause sexual dysfunction in people with schizophrenia. The authors report the effectiveness of Saikokaryukotsuboreito (Japanese traditional herbal medicine, Chai-Hu-Jia-Long-Gu-Mu-Li-Tang in Chinese) for antipsychotic-induced sexual dysfunction in two male patients with schizophrenia. The first patient was a 28-year-old man with schizophrenia who suffered erectile dysfunction induced by olanzapine 10 mg/day; the erectile dysfunction significantly improved following the treatment of Saikokaryukotsuboreito 7.5 g/day. The other case was a 43-year-old man with schizophrenia who was receiving fluphenazine decanoate at 50 mg/month and had difficulties in ejaculation; add-on of Saikokaryukotsuboreito 7.5 g/day recovered his ejaculatory function. There has been no report on the effectiveness of Japanese herbal medicine formulations for antipsychotic-induced sexual dysfunction. Although the effectiveness of Saikokaryukotsuboreito needs to be tested in systematic clinical trials, this herbal medicine may be a treatment option to consider for this annoying side effect.
Case reports in psychiatry.Case Rep Psychiatry.2014;2014:784671. doi: 10.1155/2014/784671. Epub 2014 Jan 27.
Antipsychotics sometimes cause sexual dysfunction in people with schizophrenia. The authors report the effectiveness of Saikokaryukotsuboreito (Japanese traditional herbal medicine, Chai-Hu-Jia-Long-Gu-Mu-Li-Tang in Chinese) for antipsychotic-induced sexual dysfunction in two male patients with schi
PMID 24587934

Japanese Journal

症例報告高齢者の幻覚妄想による拒食・拒薬に対する薬物療法--fluphenazine decanoateの少量投与とrisperidoneを用いて

井村徹,井村良子,山内孝之
老年精神医学雑誌 16(11), 1293-1298, 2005-11
NAID 40007046205

症例デカン酸フルフェナジンにより悪性症候群が遷延し,修正型電気けいれん療法が著効した1例

渡辺一平,三浦寛高,吉田拓 [他]
精神科 5(1), 71-75, 2004-07
NAID 40006383178

Sensitive method for the simultaneous measurement of fluphenazine decanoate and fluphenazine in plasma by high-performance liquid chromatography with coulometric detection

LUO Jiang-Ping,HUBBARD John W.,MIDHA Kamal K.
Journal of chromatography. B, Biomedical sciences and applications 688(2), 303-308, 1997-01-24
NAID 10024511244

「フルフェナジン」

Fluphenazine
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 (US)
Routes	oral, IM, decanoate
Pharmacokinetic data
Bioavailability	2.7% (Oral)
Metabolism	Hepatic
Half-life	33 hours (Oral), 14-26 days (decanoate [depot])
Excretion	bile/feces
Identifiers
CAS number	69-23-8
ATC code	N05AB02
PubChem	CID 3372
IUPHAR ligand	204
DrugBank	DB00623
ChemSpider	3255
UNII	S79426A41Z
KEGG	D07977
ChEBI	CHEBI:5123
ChEMBL	CHEMBL726
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 ; Key:PLDUPXSUYLZYBN-UHFFFAOYSA-N ;
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