perphenazine

ペルフェナジン 　

WordNet

1. tranquilizer and antidepressant (trade name Triavil) sometimes used as an antiemetic for adults (同)Triavil

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/10/25 18:16:08」(JST)

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Perphenazine

Systematic (IUPAC) name
2-[4-[3-(2-chloro-10H-phenothiazin-10-yl) propyl]piperazin-1-yl]ethanol
Clinical data
AHFS/Drugs.com	monograph
MedlinePlus	a682165
Pregnancy cat.	C (AU) C (US)
Legal status	POM (UK) ℞-only (US)
Routes	oral and i.m.
Pharmacokinetic data
Bioavailability	40%
Metabolism	hepatic
Half-life	8-12 (up to 20) hours
Excretion	?
Identifiers
CAS number	58-39-9 Y
ATC code	N05AB03
PubChem	CID 4748
IUPHAR ligand	209
DrugBank	DB00850
ChemSpider	4586 Y
UNII	FTA7XXY4EZ Y
KEGG	D00503 Y
ChEBI	CHEBI:8028 Y
ChEMBL	CHEMBL567 Y
Chemical data
Formula	C21H26ClN3OS
Mol. mass	403.97
SMILES Clc2cc1N(c3c(Sc1cc2)cccc3)CCCN4CCN(CCO)CC4
InChI InChI=1S/C21H26ClN3OS/c22-17-6-7-21-19(16-17)25(18-4-1-2-5-20(18)27-21)9-3-8-23-10-12-24(13-11-23)14-15-26/h1-2,4-7,16,26H,3,8-15H2 Y Key:RGCVKNLCSQQDEP-UHFFFAOYSA-N Y
Y (what is this?)  (verify)

Perphenazine is a typical antipsychotic drug. Chemically, it is classified as a piperazinyl phenothiazine. It has been in clinical use for decades.

Perphenazine is roughly five times as potent as chlorpromazine; thus perphenazine is considered a medium-potency antipsychotic.

Pharmacokinetics

It has an oral bioavailability of approximately 40% and a half-life of 8 to 12 hours (up to 20 hours), and is usually given in 2 or 3 divided doses each day. It is possible to give two-thirds of the daily dose at bedtime and one-third during breakfast to maximize hypnotic activity during the night and to minimize daytime sedation and hypotension without loss of therapeutic activity.

Uses

Perphenazine is used to treat psychosis (e.g. in schizophrenics) and the manic phases of bipolar disorder. Perphenazine effectively treats the positive symptoms of schizophrenia, such as hallucinations and delusions, but its effectiveness in treating the negative symptoms of schizophrenia, such as flattened affect and poverty of speech, is unclear. Earlier studies found the typical antipsychotics to be ineffective or poorly effective in the treatment of negative symptoms, but two recent, large-scale studies found no difference between perphenazine and the atypical antipsychotics.

In low doses it is used to treat agitated depression (together with an antidepressant). Fixed combinations of perphenazine and the tricyclic antidepressant amitriptyline in different proportions of weight exist (see Etrafon below). When treating depression, perphenazine is discontinued as fast as the clinical situation allows.^{[citation needed]} Perphenazine has no intrinsic antidepressive activity. Several studies show that the use of perphenazine with fluoxetine (Prozac) in patients with psychotic depression is most promising, although fluoxetine interferes with the metabolism of perphenazine, causing higher plasma levels of perphenazine and a longer half-life. In this combination the strong antiemetic action of perphenazine attenuates fluoxetine-induced nausea and vomiting (emesis), as well as the initial agitation caused by fluoxetine. Both actions can be helpful for many patients.

Perphenazine has been used in low doses as a 'normal' or 'minor' tranquilizer in patients with a known history of addiction to drugs or alcohol, a practice which is now strongly discouraged.^{[citation needed]}

Perphenazine has sedating and anxiolytic properties, making the drug useful for the treatment of agitated psychotic patients and, in high doses (up to 100 mg per day), for patients with life-threatening (febrile) catatonia, a state in which the patients are extremely agitated, but unable to express themselves. In this situation perphenazine may be used together with electroconvulsive therapy and correction of electrolytes and fluids in the body.

A valuable off-label indication is the short-time treatment of hyperemesis gravidarum, in which pregnant women experience violent nausea and vomiting. This problem can become severe enough to endanger the life of the unborn. As perphenazine has not been shown to be teratogenic and works very well, it is sometimes given orally in the smallest possible dose.

Side effects

As a member of the phenothiazine type of antipsychotics, perphenazine shares in general all allergic and toxic side-effects of chlorpromazine. A 2005 systematic review of the data on perphenazine conducted by the Cochrane Collaboration concluded that "there were no convincing differences between perphenazine and other antipsychotics" in the incidence of adverse effects. Perphenazine causes early and late extrapyramidal side effects more often than placebo, and at a similar rate to other medium-potency antipsychotics and the atypical antipsychotic risperidone.

When used for its strong antiemetic or antivertignosic effects in cases with associated brain injuries, it may obscure the clinical course and interferes with the diagnosis. High doses of perphenazine can cause temporary dyskinesia. As with other typical antipsychotics, permanent or lasting tardive dyskinesia is a risk.

Formulations

It is sold under the brand names Trilafon (single drug) and Etrafon/Triavail (contains fixed dosages of amitriptyline). A brand name in Europe is Decentan pointing to the fact that perphenazine is approximately 5-times more potent than chlorpromazine. Usual oral forms are tablets (2, 4, 8, 16 mg) and liquid concentrate (4 mg/ml).

The 'Perphenazine injectable USP' solution is intended for deep intramuscular (i.m.) injection, for patients who are not willing to take oral medication or if the patient is unable to swallow. Due to a better bioavailability of the injection, two-thirds of the original oral dose is sufficient. The incidence of hypotension, sedation and extrapyramidal side-effects may be higher compared to oral treatment. The i.m.-injections are appropriate for a few days, but oral treatment should start as soon as possible.

In many countries, depot forms of perphenazine exist (as perphenazine enanthate). One injection works for 1 to 4 weeks depending on the dose of the depot-injection. Depot-forms of perphenazine should not be used during the initial phase of treatment as the rare neuroleptic malignant syndrome may become more severe and uncontrollable with this form. Extrapyramidal side-effects may be somewhat reduced due to constant plasma-levels during depot-therapy. Also, patient compliance is sure, as many patients do not take their oral medication, particularly if feeling better once improvement in psychosis is achieved.

Interactions

Fluoxetine causes higher plasma-levels and a longer half-life of perphenazine, therefore a dose reduction of perphenazine might be necessary.

Perphenazine intensifies the central depressive action of drugs with such activity (tranquilizers, hypnotics, narcotics, antihistaminics, OTC-antiemetics etc.). A dose reduction of perphenazine or the other drug may be necessary.

The antihelmintic drug piperazine may intensify extrapyramidal side-effects. Avoid the concomitant use. Also, neurotoxic side-effects of the antibiotic streptomycin as well as of other aminoglycosids on the VIII. Brain nerve may be masked due to the strong antivertignosic effect of perphenazine. Avoid the concomitant use, too.

In general, all neuroleptics may lead to seizures in combination with the opioid tramadol (Ultram).

Perphenazine may increase the insulin needs of diabetic patients. Monitor blood glucose levels of insulin-dependent patients regularly during long-term treatment.

References

UpToDate Contents

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• 1. 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
• 2. 産後精神病の治療 treatment of postpartum psychosis
• 3. 寄生虫妄想症の治療 treatment of delusional parasitosis
• 4. 甲状腺機能正常型高サイロキシン血症および低サイロキシン血症 euthyroid hyperthyroxinemia and hypothyroxinemia
• 5. 認知症の神経精神症状のマネージメント management of neuropsychiatric symptoms of dementia

English Journal

• Field-amplified sample injection coupled with pseudo-isotachophoresis technique for sensitive determination of selected psychiatric drugs in human urine samples after dispersive liquid-liquid microextraction.

• Dziomba S1, Kowalski P2, Słomińska A1, Bączek T1.Author information 1Department of Pharmaceutical Chemistry, Medical University of Gdańsk, Hallera 107, 80-416 Gdańsk, Poland.2Department of Pharmaceutical Chemistry, Medical University of Gdańsk, Hallera 107, 80-416 Gdańsk, Poland. Electronic address: piotr.kowalski@gumed.edu.pl.AbstractA field-amplified sample injection (FASI) technique was elaborated for fast and sensitive determination of selected central nervous system drugs in human urine samples. Factors affecting the sensitivity enhancement, such as background electrolyte (BGE) and the analytical matrix composition were optimized and discussed. Pseudo-isotachophoresis (p-ITP) mechanism contribution in preconcentration mechanism was discussed. All separations were performed in uncoated fused silica capillaries 50μm×57cm at 22kV. The optimized analytical matrix was composed of 0.25mM HCOOH in 90% (v/v) methanol, while BGE contained 45mM TRIS/HCl (pH 2.20). The head-column injection was performed in 0.25mM HCOOH water solution (3s, 3.45kPa). Sample was introduced into the capillary by electrokinetic injection (70s, 5kV) followed by short BGE plug (3s, 3.45kPa). Seven psychiatric drugs (olanzapine, prochlorperazine dimaleate, trifluoperazine dihydrochloride, perphenazine, promazine hydrochloride, clomipramine hydrochloride, and chlorprothixene hydrochloride) were separated in about 6min. The elaborated method was additionally supported with dispersive liquid-liquid microextraction (DLLME) technique which in summary with FASI provided about 8000-13,000-fold sensitivity enhancement in comparison to the capillary zone electrophoresis (CZE) method with standard hydrodynamic injection (5s, 3.45kPa).
• Analytica chimica acta.Anal Chim Acta.2014 Feb 6;811:88-93. doi: 10.1016/j.aca.2013.12.021. Epub 2013 Dec 26.
• A field-amplified sample injection (FASI) technique was elaborated for fast and sensitive determination of selected central nervous system drugs in human urine samples. Factors affecting the sensitivity enhancement, such as background electrolyte (BGE) and the analytical matrix composition were opti
• PMID 24456599

• Extrapyramidal symptoms following administration of oral perphenazine 4 or 8 mg: An 11-year retrospective analysis.

• Henao JP, Peperzak KA, Lichvar AB, Orebaugh SL, Skledar SJ, Pippi MA, Williams BA.Author information From the Department of Anesthesiology, University of Pittsburgh Medical Center (JPH, KAP, SLO), School of Pharmacy (ABL, SJS), Department of Anesthesiology, University of Pittsburgh (MAP), and Department of Anesthesiology, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA (BAW) *John P. Henao and Katherin A. Peperzak are co-lead authors for the article.AbstractBACKGROUND: Perphenazine is a treatment option in postoperative nausea and vomiting (PONV) prophylaxis. Chronic administration and high dose are known to cause extrapyramidal system (EPS) dysfunction at a frequency of 8%, but the incidence of acute EPS after a single 4 or 8 mg dose is unknown.
• European journal of anaesthesiology.Eur J Anaesthesiol.2014 Feb 5. [Epub ahead of print]
• BACKGROUND: Perphenazine is a treatment option in postoperative nausea and vomiting (PONV) prophylaxis. Chronic administration and high dose are known to cause extrapyramidal system (EPS) dysfunction at a frequency of 8%, but the incidence of acute EPS after a single 4 or 8 mg dose is unknown.OBJE
• PMID 24503705

• Phenothiazines induce PP2A-mediated apoptosis in T cell acute lymphoblastic leukemia.

• Gutierrez A, Pan L, Groen RW, Baleydier F, Kentsis A, Marineau J, Grebliunaite R, Kozakewich E, Reed C, Pflumio F, Poglio S, Uzan B, Clemons P, Verplank L, An F, Burbank J, Norton S, Tolliday N, Steen H, Weng AP, Yuan H, Bradner JE, Mitsiades C, Look AT, Aster JC.AbstractT cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer that is frequently associated with activating mutations in NOTCH1 and dysregulation of MYC. Here, we performed 2 complementary screens to identify FDA-approved drugs and drug-like small molecules with activity against T-ALL. We developed a zebrafish system to screen small molecules for toxic activity toward MYC-overexpressing thymocytes and used a human T-ALL cell line to screen for small molecules that synergize with Notch inhibitors. We identified the antipsychotic drug perphenazine in both screens due to its ability to induce apoptosis in fish, mouse, and human T-ALL cells. Using ligand-affinity chromatography coupled with mass spectrometry, we identified protein phosphatase 2A (PP2A) as a perphenazine target. T-ALL cell lines treated with perphenazine exhibited rapid dephosphorylation of multiple PP2A substrates and subsequent apoptosis. Moreover, shRNA knockdown of specific PP2A subunits attenuated perphenazine activity, indicating that PP2A mediates the drug's antileukemic activity. Finally, human T-ALLs treated with perphenazine exhibited suppressed cell growth and dephosphorylation of PP2A targets in vitro and in vivo. Our findings provide a mechanistic explanation for the recurring identification of phenothiazines as a class of drugs with anticancer effects. Furthermore, these data suggest that pharmacologic PP2A activation in T-ALL and other cancers driven by hyperphosphorylated PP2A substrates has therapeutic potential.
• The Journal of clinical investigation.J Clin Invest.2014 Feb 3;124(2):644-55. doi: 10.1172/JCI65093. Epub 2014 Jan 9.
• T cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer that is frequently associated with activating mutations in NOTCH1 and dysregulation of MYC. Here, we performed 2 complementary screens to identify FDA-approved drugs and drug-like small molecules with activity against T-ALL. We deve
• PMID 24401270

Japanese Journal

• Development and validation of a gas chromatographic-mass spectrometric method for quantitative determination of perphenazine in rabbit plasma after sublingual administration

• TURUNEN Elina,LEHTONEN Marko,JARVINEN Tomi,JARHO Pekka
• Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 872(1), 51-57, 2008-09-01
• NAID 10028005618

• HPLC quantification of perphenazine in sheep plasma : Application to a pharmacokinetic study

• PEDERNERA Cecilia,RUIZ Jose Luis,CASTELLS Gloria,MANTECA Xavier,CRISTOFOL Carles
• Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 854(1), 308-312, 2007-07-01
• NAID 10025805645

• Simple and simultaneous determination for 12 phenothiazines in human serum by reversed-phase high-performance liquid chromatography

• TANAKA Einosuke,NAKAMURA Takako,TERADA Masaru,SHINOZUKA Tatsuo,HASHIMOTO Chikako,KURIHARA Katsuyoshi,HONDA Katsuya
• Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 854(1), 116-120, 2007-07-01
• … A high-performance liquid chromatographic method has been developed for the simultaneous analysis of the 12 phenothiazines (chlorpromazine, fluphenazine, levomepromazine, perazine, perphenazine, prochlorperazine, profenamine, promethazine, propericiazine, thioproperazine, thioridazine and trifluoperazine) in human serum using HPLC/UV. …
• NAID 10025805017

Related Links

• perphenazine - definition of perphenazine by Medical dictionary

perphenazine /per·phen·a·zine/ (-fen´ah-zēn) a phenothiazine used as an antipsychotic and as an antiemetic. per·phen·a·zine (p r-f n-z n) n. A crystalline compound used as a tranquilizer especially in the treatment of psychosis and to ...

• Perphenazine: MedlinePlus Drug Information

Before taking perphenazine, tell your doctor and pharmacist if you are allergic to perphenazine; other phenothiazines such as chlorpromazine, fluphenazine, prochlorperazine (Compazine), promethazine (Phenergan ...

Related Pictures

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★リンクテーブル★

リンク元	「フェノチアジン誘導体」「ペルフェナジン」「Trilafon」
拡張検索	「perphenazine fendizoate」「perphenazine hydrochloride」

「フェノチアジン誘導体」

　　[★]

英

phenothiazine derivative, phenothiazines

関

フェノチアジン phenothiazine、抗精神病薬

• フェノチアジン核/骨格を有する化合物

作用機序

• D2受容体拮抗

適応

• 抗精神病薬：統合失調症、躁病

副作用

• 錐体外路症状、意識障害、血圧低下(自律神経遮断作用による？)

所属する薬物

• 抗精神病薬

• クロルプロマジン chlorpromazine (コントミン、ベゲタミン-A配合)
• チオリダジン thioridazine(メレリル)
• レボメプロマジン levomepromazine(ヒルナミン)
• プロペリシアジン propericiazine(ニューレプチル)
• フルフェナジン fluphenazine(フルデカシン、フルメジン)
• ペルフェナジン perphenazine(トリラホン)
• トリフロペラジン trifluoperazine

「ペルフェナジン」

　　[★]

英

perphenazine

ラ

perphenazinum

同

クロルピプラジン chlorpiprazine

化

マレイン酸ペルフェナジン perphenazine maleate perphenazini maleas

商

トリオミン、トリラホン Trilafon、ピーゼットシー

「Trilafon」

　　[★]

トリラホン

関

perphenazine

「perphenazine fendizoate」

　　[★]

• フェンジゾ酸ペルフェナジン

関

perphenazine、perphenazine hydrochloride、perphenazine maleate

「perphenazine hydrochloride」

　　[★]

• 塩酸ペルフェナジン

関

perphenazine、perphenazine fendizoate、perphenazine maleate