Pizotifen

The main medical use for pizotifen is for the prevention of migraine and cluster headache. Pizotifen is one of a range of medications used for this purpose, other options include propranolol, topiramate, valproic acid, cyproheptadine and amitriptyline. While pizotifen is effective in adults,{{cite journal | vauthors = Jackson JL, Cogbill E, Santana-Davila R, Eldredge C, Collier W, Gradall A, Sehgal N, Kuester J | display-authors = 6 | title = A Comparative Effectiveness Meta-Analysis of Drugs for the Prophylaxis of Migraine Headache | journal = PLOS ONE | volume = 10 | issue = 7 | pages = e0130733 | date = 2015-07-14 | pmid = 26172390 | pmc = 4501738 | doi = 10.1371/journal.pone.0130733 | doi-access = free | bibcode = 2015PLoSO..1030733J }} evidence of efficacy in children is limited,{{cite journal | vauthors = Barnes N, Millman G | title = Do pizotifen or propranolol reduce the frequency of migraine headache? | journal = Archives of Disease in Childhood | volume = 89 | issue = 7 | pages = 684–685 | date = July 2004 | pmid = 15210509 | pmc = 1719986 | doi = 10.1136/adc.2004.054668 }} and its use is limited by side effects, principally drowsiness and weight gain, and it is usually not the first choice medicine for preventing migraines, instead being used as an alternative when other drugs have failed to be effective.{{cite journal | vauthors = Pierangeli G, Cevoli S, Sancisi E, Grimaldi D, Zanigni S, Montagna P, Cortelli P | title = Which therapy for which patient? | journal = Neurological Sciences | volume = 27 | issue = Suppl 2 | pages = S153–S158 | date = May 2006 | pmid = 16688621 | doi = 10.1007/s10072-006-0592-0 | s2cid = 24217802 }} It is not effective in relieving migraine attacks once in progress.

Pizotifen has also been reported as highly effective in a severe case of erythromelalgia, a rare neurovascular disease that is sometimes refractory to the other drugs named above.{{cite journal | vauthors = Cohen JS | title = Erythromelalgia: new theories and new therapies | journal = Journal of the American Academy of Dermatology | volume = 43 | issue = 5 Pt 1 | pages = 841–847 | date = November 2000 | pmid = 11050591 | doi = 10.1067/mjd.2000.109301 | s2cid = 40807034 }}

Other applications for which pizotifen may be used include as an antidepressant, or for the treatment of anxiety or social phobia.{{cite journal | vauthors = Standal JE | title = Pizotifen as an antidepressant | journal = Acta Psychiatrica Scandinavica | volume = 56 | issue = 4 | pages = 276–279 | date = October 1977 | pmid = 335788 | doi = 10.1111/j.1600-0447.1977.tb00228.x | s2cid = 6445059 }}{{cite journal | vauthors = Banki CM | title = Clinical observations with pizotifene (Sandomigran) in the treatment of nonmigrainous depressed women | journal = Archiv für Psychiatrie und Nervenkrankheiten | volume = 225 | issue = 1 | pages = 67–72 | date = March 1978 | pmid = 348154 | doi = 10.1007/bf00367352 | s2cid = 13510725 }} Animal studies also suggest that pizotyline could be used in the treatment of serotonin syndrome or MDMA overdose{{cite journal | vauthors = Young R, Khorana N, Bondareva T, Glennon RA | title = Pizotyline effectively attenuates the stimulus effects of N-methyl-3,4-methylenedioxyamphetamine (MDMA) | journal = Pharmacology, Biochemistry, and Behavior | volume = 82 | issue = 2 | pages = 404–410 | date = October 2005 | pmid = 16253319 | doi = 10.1016/j.pbb.2005.09.010 | s2cid = 20885754 }} in a similar manner to the closely related antihistamine/anti-serotonin medication cyproheptadine.

Pizotifen might be useful as a hallucinogen antidote or "trip killer" in blocking the effects of serotonergic psychedelics like psilocybin.{{cite journal | vauthors = Halman A, Kong G, Sarris J, Perkins D | title = Drug-drug interactions involving classic psychedelics: A systematic review | journal = J Psychopharmacol | volume = 38 | issue = 1 | pages = 3–18 | date = January 2024 | pmid = 37982394 | pmc = 10851641 | doi = 10.1177/02698811231211219 | url = }} It might also be useful in the treatment of MDMA overdose.

Caution is required in patients having closed angle glaucoma and in patients with a predisposition to urinary retention as the medication exhibits a relatively small anticholinergic effect. Dose adjustment is required in people who have chronic kidney disease. Liver injury has also been reported. Pizotifen treatment should be discontinued if there is any clinical evidence of liver dysfunction during treatment. Caution is advised in patients having a history of epilepsy.

Withdrawal symptoms like depression, tremor, nausea, anxiety, malaise, dizziness, sleep disorder and weight decrease have been reported following abrupt cessation of pizotifen.{{cite web|url=https://www.medsafe.govt.nz/profs/datasheet/s/Sandomigrantab.pdf|title=SANDOMIGRAN® pizotifen 500 micrograms coated tablets | work = AFT Pharmaceuticals Ltd | date = 21 June 2019 | publisher = Medsafe: New Zealand Medicines and Medical Devices Safety }}

Pizotifen is contraindicated in patients who suffer from hypersensitivity to any of its components or have gastric outlet obstruction, angle-closure glaucoma, and difficulty urinating.{{cite web |title=Pizotifen |url=http://lekarstwo.ru/en/preparati/pizotifen.html |work=Universal Reference Book of Medicines |via=Likarstwo.ru |ref=Uref}} In addition, women who are pregnant should not take pizotifen.

Side effects include sedation, dry mouth, drowsiness, increased appetite and weight gain.Crowder D, Maclay WP. Pizotifen once daily in the prophylaxis of migraine: results of a multi-centre general practice study. Current Medical Research and Opinion. 1984;9(4):280-5. Occasionally it may cause nausea, headaches, or dizziness. In rare cases, anxiety, aggression and depression may also occur.

Pizotifen is a serotonin antagonist acting mainly at the 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors. It also has some activity as an antihistamine as well as some anticholinergic activity.{{cite journal | vauthors = Dixon AK, Hill RC, Roemer D, Scholtysik G | title = Pharmacological properties of 4(1-methyl-4-piperidylidine)-9,10-dihydro-4H-benzo-[4,5]cyclohepta[1,2]-thiophene hydrogen maleate (pizotifen) | journal = Arzneimittel-Forschung | volume = 27 | issue = 10 | pages = 1968–1979 | date = 1977 | pmid = 411500 }} The drug binds non-selectivey to many targets, including serotonin, dopamine, adrenergic, histamine, and muscarinic acetylcholine receptors.

Pizotifen is able to dose-dependently and fully antagonize the discriminative stimulus effects of the serotonin–norepinephrine–dopamine releasing agent and serotonin 5-HT₂ receptor agonist MDMA in rodent drug discrimination tests. Conversely, the related drug cyproheptadine was only partially effective and clozapine was ineffective. All three of these agents, pizotifen, cyproheptadine, and clozapine act as non-selective monoamine receptor antagonists. Pizotifen also fully blocks the effects of serotonergic psychedelics, including LSD, mescaline, 5-MeO-DMT, and DOM, in drug discrimination tests.

The antimigraine activity of pizotifen might be specifically due to serotonin 5-HT_2B receptor blockade.{{cite journal | vauthors = Segelcke D, Messlinger K | title = Putative role of 5-HT2B receptors in migraine pathophysiology | journal = Cephalalgia | volume = 37 | issue = 4 | pages = 365–371 | date = April 2017 | pmid = 27127104 | doi = 10.1177/0333102416646760 | url = }}

Pizotifen is a tricyclic compound and is specifically a benzocycloheptene.

Close analogues of pizotifen include ketotifen and cyproheptadine, among others.

Pizotifen was first described in the literature by 1964.

Pizotifen is the generic name of the drug and its {{Abbrlink|INN|International Nonproprietary Name}} and {{Abbrlink|BAN|British Approved Name}}, while pizotyline is its {{Abbrlink|USAN|United States Adopted Name}}.{{cite book | vauthors = Elks J | title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies | publisher=Springer US | year=2014 | isbn=978-1-4757-2085-3 | url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA1002 | access-date=24 November 2024 | page=1002}}{{cite book | author=Schweizerischer Apotheker-Verein | title=Index Nominum: International Drug Directory | publisher=Medpharm Scientific Publishers | year=2004 | isbn=978-3-88763-101-7 | url=https://books.google.com/books?id=EgeuA47Ocm4C&pg=PA992 | access-date=24 November 2024 | page=992}}{{cite book | vauthors = Morton IK, Hall JM | title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms | publisher=Springer Netherlands | year=2012 | isbn=978-94-011-4439-1 | url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA225 | access-date=24 November 2024 | page=225}} Brand names of pizotifen include Sandomigran, Mosegor, and Litec, among others.

Pizotifen is available widely throughout the world, including in Europe.{{cite web | title=Pizotifen (International database) | website=Drugs.com | date=3 November 2024 | url=https://www.drugs.com/international/pizotifen.html | access-date=24 November 2024}}

{{Reflist}}

• [http://www.medsafe.govt.nz/profs/datasheet/s/Sandomigrantab.pdf Sandomigran drug data sheet]

{{Antimigraine preparations}}

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