Pizotifen

Overview

Pizotifen, also known as pizotyline and sold under the brand names Sandomigran and Mosegor among others, is an antimigraine agent of the tricyclic group which is used primarily as a preventative to reduce the frequency of recurrent migraine headaches.[1] WP

Uses, dosage and effects

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.[2][3][4] WP

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.[5] WP

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.[6][7][8] WP

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.[8][9] WP

Risks and side effects

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.[10] WP

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.[11] WP

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.[12] WP

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.[8][13][14] WP

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.[8] WP

The antimigraine activity of pizotifen might be specifically due to serotonin 5-HT2B receptor blockade.[15] WP

Pharmacokinetics

The elimination half-life of pizotifen is 23 hours.[16][17] WP

History

History

Pizotifen was first described in the literature by 1964.[18] WP

Legal status

Names

Pizotifen is the generic name of the drug and its INN (International Nonproprietary Name) and BAN (British Approved Name), while pizotyline is its USAN (United States Adopted Name). Brand names of pizotifen include Sandomigran, Mosegor, and Litec, among others.[18–21] WP

Availability

Pizotifen is available widely throughout the world, including in Europe.[19][21] WP

Chemistry

Formula

C19H21NS PC

CAS number

15574-96-6 PC

Molar mass (g/mol)

295.4 PC

IUPAC name (computed by PubChem)

1-methyl-4-(6-thiatricyclo[8.4.0.03,7]tetradeca-1(14),3(7),4,10,12-pentaen-2-ylidene)piperidine PC

SMILES

CN1CCC(=C2C3=C(CCC4=CC=CC=C42)SC=C3)CC1 PC

InChIKey

FIADGNVRKBPQEU-UHFFFAOYSA-N PC

PubChem CID

27400

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Stark RJ, Valenti L, Miller GC. Management of migraine in Australian general practice. The Medical Journal of Australia. August 2007. doi:10.5694/j.1326-5377.2007.tb01170.x · PMID 17680738
2. Journal / agency Jackson JL, Cogbill E, Santana-Davila R, Eldredge C, Collier W, Gradall A, Sehgal N, Kuester J. A Comparative Effectiveness Meta-Analysis of Drugs for the Prophylaxis of Migraine Headache. PLOS ONE. 2015-07-14. doi:10.1371/journal.pone.0130733 · PMID 26172390 · PMC4501738
3. Journal / agency Barnes N, Millman G. Do pizotifen or propranolol reduce the frequency of migraine headache?. Archives of Disease in Childhood. July 2004. doi:10.1136/adc.2004.054668 · PMID 15210509 · PMC1719986
4. Journal / agency Pierangeli G, Cevoli S, Sancisi E, Grimaldi D, Zanigni S, Montagna P, Cortelli P. Which therapy for which patient?. Neurological Sciences. May 2006. doi:10.1007/s10072-006-0592-0 · PMID 16688621
5. Journal / agency Cohen JS. Erythromelalgia: new theories and new therapies. Journal of the American Academy of Dermatology. November 2000. doi:10.1067/mjd.2000.109301 · PMID 11050591
6. Journal / agency Standal JE. Pizotifen as an antidepressant. Acta Psychiatrica Scandinavica. October 1977. doi:10.1111/j.1600-0447.1977.tb00228.x · PMID 335788
7. Journal / agency Banki CM. Clinical observations with pizotifene (Sandomigran) in the treatment of nonmigrainous depressed women. Archiv für Psychiatrie und Nervenkrankheiten. March 1978. doi:10.1007/bf00367352 · PMID 348154
8. Journal / agency Young R, Khorana N, Bondareva T, Glennon RA. Pizotyline effectively attenuates the stimulus effects of N-methyl-3,4-methylenedioxyamphetamine (MDMA). Pharmacology, Biochemistry, and Behavior. October 2005. doi:10.1016/j.pbb.2005.09.010 · PMID 16253319
9. Journal / agency Halman A, Kong G, Sarris J, Perkins D. Drug-drug interactions involving classic psychedelics: A systematic review. J Psychopharmacol. January 2024. doi:10.1177/02698811231211219 · PMID 37982394 · PMC10851641
10. Other SANDOMIGRAN® pizotifen 500 micrograms coated tablets. 21 June 2019
11. Other Pizotifen
12. Other 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
13. Journal / agency Dixon AK, Hill RC, Roemer D, Scholtysik G. Pharmacological properties of 4(1-methyl-4-piperidylidine)-9,10-dihydro-4H-benzo-[4,5]cyclohepta[1,2]-thiophene hydrogen maleate (pizotifen). Arzneimittel-Forschung. 1977. PMID 411500
14. Journal / agency Newman-Tancredi A, Conte C, Chaput C, Verrièle L, Audinot-Bouchez V, Lochon S, Lavielle G, Millan MJ. Agonist activity of antimigraine drugs at recombinant human 5-HT1A receptors: potential implications for prophylactic and acute therapy. Naunyn Schmiedebergs Arch Pharmacol. June 1997. doi:10.1007/pl00005000 · PMID 9205951
15. Journal / agency Segelcke D, Messlinger K. Putative role of 5-HT2B receptors in migraine pathophysiology. Cephalalgia. April 2017. doi:10.1177/0333102416646760 · PMID 27127104
16. Harm reduction site Pizotifen: Uses, Interactions, Mechanism of Action. 1 January 1975
17. Other PRODUCT MONOGRAPH INCLUDING PATIENT MEDICATION INFORMATION: PrSANDOMIGRAN DS: Pizotifen tablets
18. Other Elks J. The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. 2014
19. Other Schweizerischer Apotheker-Verein. Index Nominum: International Drug Directory. 2004
20. Other Morton IK, Hall JM. Concise Dictionary of Pharmacological Agents: Properties and Synonyms. 2012
21. Other Pizotifen (International database). 3 November 2024

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