Pizotifen

Medical uses

Migraine headaches

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, evidence of efficacy in children is limited, 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. It is not effective in relieving migraine attacks once in progress.

Other uses

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.

Other applications for which pizotifen may be used include as an antidepressant, or for the treatment of anxiety or social phobia. Animal studies also suggest that pizotyline could be used in the treatment of serotonin syndrome or MDMA overdose 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. It might also be useful in the treatment of MDMA overdose.

Contraindications

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.

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. In addition, women who are pregnant should not take pizotifen.

Adverse effects

Side effects include sedation, dry mouth, drowsiness, increased appetite and weight gain. Occasionally it may cause nausea, headaches, or dizziness. In rare cases, anxiety, aggression and depression may also occur.

Pharmacology

Pharmacodynamics

Pizotifen is a serotonin antagonist acting mainly at the 5-HT2A, 5-HT2B, and 5-HT2C receptors. It also has some activity as an antihistamine as well as some anticholinergic activity. The drug binds non-selectively to many targets, including serotonin, dopamine, adrenergic, histamine, and muscarinic acetylcholine receptors. Besides its serotonin 5-HT2 receptor antagonism, pizotifen is a low-potency moderate-efficacy partial agonist of the serotonin 5-HT1A receptor.

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-HT2B receptor blockade.

Pharmacokinetics

The elimination half-life of pizotifen is 23hours.

Chemistry

Pizotifen is a tricyclic compound and is specifically a benzocycloheptene.

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

History

Pizotifen was first described in the literature by 1964.

Society and culture

Names

Pizotifen is the generic name of the drug and its and , while pizotyline is its . Brand names of pizotifen include Sandomigran, Mosegor, and Litec, among others.

Availability

Pizotifen is available widely throughout the world, including in Europe.

References

References

1. (1 January 1975). "Pizotifen: Uses, Interactions, Mechanism of Action".
2. https://pdf.hres.ca/dpd_pm/00072170.PDF
3. (August 2007). "Management of migraine in Australian general practice". The Medical Journal of Australia.
4. (2015-07-14). "A Comparative Effectiveness Meta-Analysis of Drugs for the Prophylaxis of Migraine Headache". PLOS ONE.
5. (July 2004). "Do pizotifen or propranolol reduce the frequency of migraine headache?". Archives of Disease in Childhood.
6. (May 2006). "Which therapy for which patient?". Neurological Sciences.
7. (November 2000). "Erythromelalgia: new theories and new therapies". Journal of the American Academy of Dermatology.
8. (October 1977). "Pizotifen as an antidepressant". Acta Psychiatrica Scandinavica.
9. (March 1978). "Clinical observations with pizotifene (Sandomigran) in the treatment of nonmigrainous depressed women". Archiv für Psychiatrie und Nervenkrankheiten.
10. (October 2005). "Pizotyline effectively attenuates the stimulus effects of N-methyl-3,4-methylenedioxyamphetamine (MDMA)". Pharmacology, Biochemistry, and Behavior.
11. (January 2024). "Drug-drug interactions involving classic psychedelics: A systematic review". J Psychopharmacol.
12. (21 June 2019). "SANDOMIGRAN® pizotifen 500 micrograms coated tablets". Medsafe: New Zealand Medicines and Medical Devices Safety.
13. "Pizotifen". Universal Reference Book of Medicines.
14. 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.
15. "PDSP Database".
16. "PDSP Database".
17. "BindingDB BDBM82088 CAS_15574-96-6::NSC_27400::PIZOTIFEN".
18. (October 2005). "Pizotyline effectively attenuates the stimulus effects of N-methyl-3,4-methylenedioxyamphetamine (MDMA)". Pharmacol Biochem Behav.
19. (December 2013). "Synthesis and structure-activity relationships of new carbonyl guanidine derivatives as novel dual 5-HT2B and 5-HT7 receptor antagonists". Bioorg Med Chem.
20. (June 1997). "Agonist activity of antimigraine drugs at recombinant human 5-HT1A receptors: potential implications for prophylactic and acute therapy". Naunyn Schmiedebergs Arch Pharmacol.
21. (1977). "Pharmacological properties of 4(1-methyl-4-piperidylidine)-9,10-dihydro-4H-benzo-[4,5]cyclohepta[1,2]-thiophene hydrogen maleate (pizotifen)". Arzneimittel-Forschung.
22. (April 2017). "Putative role of 5-HT2B receptors in migraine pathophysiology". Cephalalgia.
23. (2014). "The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies". Springer US.
24. Schweizerischer Apotheker-Verein. (2004). "Index Nominum: International Drug Directory". Medpharm Scientific Publishers.
25. (2012). "Concise Dictionary of Pharmacological Agents: Properties and Synonyms". Springer Netherlands.
26. (3 November 2024). "Pizotifen (International database)".