Chemistry:Fluphenazine
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| Trade names | Prolixin, Modecate, Moditen others |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a682172 |
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| Routes of administration | By mouth, Intramuscular injection, depot injection (fluphenazine decanoate) |
| Drug class | Typical antipsychotic |
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| Bioavailability | 2.7% (by mouth) |
| Metabolism | unclear[1] |
| Elimination half-life | IM 15 hours (HCL), 7–10 days (decanoate)[1] |
| Excretion | Urine, feces |
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| Formula | C22H26F3N3OS |
| Molar mass | 437.53 g·mol−1 |
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Fluphenazine, sold under the brand name Prolixin among others, is a high-potency typical antipsychotic medication.[1] It is used in the treatment of chronic psychoses such as schizophrenia,[1][2] and appears to be about equal in effectiveness to low-potency antipsychotics like chlorpromazine.[3] It is given by mouth, injection into a muscle, or just under the skin.[1] There is also a long acting injectable version that may last for up to four weeks.[1] Fluphenazine decanoate, the depot injection form of fluphenazine, should not be used by people with severe depression.[4]
Common side effects include movement problems, sleepiness, depression and increased weight.[1] Serious side effects may include neuroleptic malignant syndrome, low white blood cell levels, and the potentially permanent movement disorder tardive dyskinesia.[1] In older people with psychosis as a result of dementia it may increase the risk of dying.[1] It may also increase prolactin levels which may result in milk production, enlarged breasts in males, impotence, and the absence of menstrual periods.[1] It is unclear if it is safe for use in pregnancy.[1]
Fluphenazine is a typical antipsychotic of the phenothiazine class.[1] Its mechanism of action is not entirely clear but believed to be related to its ability to block dopamine receptors.[1] In up to 40% of those on long term phenothiazines, liver function tests become mildly abnormal.[5]
Fluphenazine came into use in 1959.[6] The injectable form is on the World Health Organization's List of Essential Medicines.[7] It is available as a generic medication.[1] It was discontinued in Australia in 2017.[8]
Medical use
A 2018 Cochrane review found that fluphenazine was an imperfect treatment and other inexpensive drugs less associated with side effects may be an equally effective choice for people with schizophrenia.[9]
Side effects
Discontinuation
The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse.[10] Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.[11] Other symptoms may include restlessness, increased sweating, and trouble sleeping.[11] Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.[11] Symptoms generally resolve after a short period of time.[11]
There is tentative evidence that discontinuation of antipsychotics can result in psychosis.[12] It may also result in reoccurrence of the condition that is being treated.[13] Rarely tardive dyskinesia can occur when the medication is stopped.[11]
Pharmacology
Pharmacodynamics
Fluphenazine acts primarily by blocking post-synaptic D2 receptors in the basal ganglia, cortical and limbic system. It also blocks alpha-1 adrenergic receptors, muscarinic-1 receptors, and histamine-1 receptors.[14][15]
| Site | Ki (nM) | Action | Ref |
|---|---|---|---|
| 5-HT1A | 145-2829 | ND | [16] |
| 5-HT1B | 334 | ND | [16] |
| 5-HT1D | 334 | ND | [16] |
| 5-HT1E | 540 | ND | [16] |
| 5-HT2A | 3.8-98 | ND | [16] |
| 5-HT2B | ND | ND | [16] |
| 5-HT2C | 174–2,570 | ND | [16] |
| 5-HT3 | 4,265- > 10,000 | ND | [16] |
| 5-HT5A | 145 | ND | [16] |
| 5-HT6 | 7.9 - 38 | ND | [16] |
| 5-HT7 | 8 | ND | [16] |
| D1 | 14.45 | ND | [16] |
| D2 | 0.89 | ND | |
| D2L | ND | [16] | |
| D3 | 1.412 | ND | [16] |
| D4 | 89.12 | ND | [16] |
| D5 | 95–2,590 | ND | [16] |
| α1A | 6.4-9 | ND | [16] |
| α1B | 13 | ND | [16] |
| α2A | 304-314 | ND | [16] |
| α2B | 181.6-320 | ND | [16] |
| α2C | 28.8-122 | ND | [16] |
| β1 | > 10,000 | ND | [16] |
| β2 | > 10,000 | ND | [16] |
| H1 | 7.3-70 | ND | [16] |
| H2 | 560 | ND | [16] |
| H3 | 1,000 | ND | [16] |
| H4 | > 10,000 | ND | [16] |
| M1 | 1,095-3,235.93 | ND | [16] |
| M2 | 2,187.76-7,163 | ND | [16] |
| M3 | 1441–1445.4 | ND | [16] |
| M4 | 5,321 | ND | [16] |
| M5 | 357 | ND | [16] |
| SERT | ND | ND | [16] |
| NET | ND | ND | [16] |
| DAT | ND | ND | [16] |
| NMDA (PCP) |
ND | ND | [16] |
| Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site. All data are for human cloned proteins, except 5-HT3 (rat), D4 (human/rat), H3 (guinea pig), and NMDA/PCP (rat).[16] | |||
Pharmacokinetics
History
Fluphenazine came into use in 1959.[6]
Availability
The injectable form is on the World Health Organization's List of Essential Medicines.[7] It is available as a generic medication.[1] It was discontinued in Australia in 2017.[8]
Veterinary
In horses, it is sometimes given by injection as an anxiety-relieving medication, though there are many negative common side effects and it is forbidden by many equestrian competition organizations.[17]
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 "fluphenazine decanoate". The American Society of Health-System Pharmacists. https://www.drugs.com/monograph/fluphenazine-decanoate.html.
- ↑ "Product Information: Modecate (Fluphenazine Decanoate Oily Injection )" (PDF). TGA eBusiness Services. Bristol-Myers Squibb Australia Pty Ltd. 1 November 2012. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-02643-3.
- ↑ "Fluphenazine versus low-potency first-generation antipsychotic drugs for schizophrenia". The Cochrane Database of Systematic Reviews 8 (8): CD009230. August 2014. doi:10.1002/14651858.CD009230.pub2. PMID 25087165.
- ↑ "Modecate Injection 25mg/ml - Patient Information Leaflet (PIL) - (eMC)" (in en). http://www.medicines.org.uk/emc/medicine/15355/PIL/Modecate+Injection+25mg+ml.
- ↑ "Fluphenazine". https://livertox.nih.gov/Fluphenazine.htm.
- ↑ 6.0 6.1 Pharmaceutical Manufacturing Encyclopedia. (3rd ed.). Burlington: Elsevier. 2007. p. 1680. ISBN 9780815518563. https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA1680.
- ↑ 7.0 7.1 World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. 2019. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
- ↑ 8.0 8.1 "Fluphenazine - Australian Medicines Handbook". Australian Medicines Handbook. Australian Medicines Handbook Pty Ltd. July 2017. https://amhonline.amh.net.au/chapters/chap-18/antipsychotics/fluphenazine.
- ↑ "Fluphenazine (oral) versus placebo for schizophrenia". The Cochrane Database of Systematic Reviews 6 (7): CD006352. June 2018. doi:10.1002/14651858.CD006352.pub3. PMID 29893410.
- ↑ Joint Formulary Committee, BMJ, ed (March 2009). "4.2.1". British National Formulary (57 ed.). United Kingdom: Royal Pharmaceutical Society of Great Britain. p. 192. ISBN 978-0-85369-845-6. "Withdrawal of antipsychotic drugs after long-term therapy should always be gradual and closely monitored to avoid the risk of acute withdrawal syndromes or rapid relapse."
- ↑ 11.0 11.1 11.2 11.3 11.4 (in en) Adverse Syndromes and Psychiatric Drugs: A Clinical Guide. OUP Oxford. 2004. pp. 207–216. ISBN 9780198527480. https://books.google.com/books?id=CWR7DwAAQBAJ&pg=PA207.
- ↑ "Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal-related relapse". Acta Psychiatrica Scandinavica 114 (1): 3–13. July 2006. doi:10.1111/j.1600-0447.2006.00787.x. PMID 16774655.
- ↑ (in en) Adherence to Antipsychotics in Schizophrenia. Springer Science & Business Media. 2013. p. 85. ISBN 9788847026797. https://books.google.com/books?id=odE-AgAAQBAJ&pg=PA85.
- ↑ "Fluphenazine". StatPearls. 2020. PMID 29083807. https://www.ncbi.nlm.nih.gov/books/NBK459194/.
- ↑ "Fluphenazine" (in en). PubChem. U.S. National Library of Medicine. https://pubchem.ncbi.nlm.nih.gov/compound/3372.
- ↑ 16.00 16.01 16.02 16.03 16.04 16.05 16.06 16.07 16.08 16.09 16.10 16.11 16.12 16.13 16.14 16.15 16.16 16.17 16.18 16.19 16.20 16.21 16.22 16.23 16.24 16.25 16.26 16.27 16.28 16.29 16.30 16.31 16.32 16.33 16.34 16.35 16.36 Cite error: Invalid
<ref>tag; no text was provided for refs namedPDSP - ↑ "Effects of Behavior-Modifying Drug Investigated (AAEP 2011)". The Horse Media Group. 31 March 2012. http://www.thehorse.com/articles/28907/effects-of-behavior-modifying-drug-investigated-aaep-2011.
External links
- "Fluphenazine". Drug Information Portal. U.S. National Library of Medicine. https://druginfo.nlm.nih.gov/drugportal/name/fluphenazine.
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