Pizotifen

Pizotifen (INN) or pizotyline (USAN), trade name Sandomigran, is a benzocycloheptene-based drug used as a medicine, primarily as a preventive to reduce the frequency of recurrent migraine headaches.^[1]

Pizotifen

Clinical data
Trade names	Sandomigran
AHFS/Drugs.com	International Drug Names
Pregnancy category	AU: B1
Routes of administration	Oral
ATC code	N02CX01 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) CA: ℞-only UK: POM (Prescription only)
Pharmacokinetic data
Bioavailability	78%
Protein binding	91%
Metabolism	Glucuronidation (main route). N-glucuronide accounts for >50% of plasma and 60–70% of urinary excreted drug
Elimination half-life	23 hours
Excretion	18% feces, 55% urine (both as metabolites)
Identifiers
IUPAC name 4-(1-methyl-4-piperidylidine)-9,10-dihydro -4H-benzo-[4,5]cyclohepta[1,2]-thiophene
CAS Number	15574-96-6 N
PubChem CID	27400
IUPHAR/BPS	93
DrugBank	DB06153 Y
ChemSpider	25497 Y
UNII	0BY8440V3N
KEGG	D05523 Y
ChEMBL	ChEMBL294951 Y
CompTox Dashboard (EPA)	DTXSID6023490
ECHA InfoCard	100.036.014
Chemical and physical data
Formula	C19H21NS
Molar mass	295.44 g·mol−1
3D model (JSmol)	Interactive image
SMILES s1c3c(cc1)C(\c2c(cccc2)CC3)=C4/CCN(C)CC4
InChI InChI=1S/C19H21NS/c1-20-11-8-15(9-12-20)19-16-5-3-2-4-14(16)6-7-18-17(19)10-13-21-18/h2-5,10,13H,6-9,11-12H2,1H3 Y Key:FIADGNVRKBPQEU-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Uses

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,^[2] evidence of efficacy in children is limited,^[3] 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.^[4] 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.^[5]

Other applications for which pizotifen may be used include as an antidepressant, or for the treatment of anxiety or social phobia.^[6][7] Animal studies also suggest that pizotyline could be used in the treatment of serotonin syndrome or MDMA overdose^[8] in a similar manner to the closely related antihistamine/antiserotonin medication cyproheptadine.

Pizotifen might be useful as a hallucinogen antidote or "trip killer" in blocking the effects of serotonergic psychedelics like psilocybin.^[9]

Adverse effects

Side effects include sedation, dry mouth, drowsiness, increased appetite and weight gain.^[10] Occasionally it may cause nausea, headaches, or dizziness. In rare cases, anxiety, aggression and depression may also occur.

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.^[11] Pizotifen is contraindicated in patients who suffer from hypersensitivity to any of its components, also Pizotifen is contraindicated in gastric outlet obstruction, pregnancy, angle-closure glaucoma and difficulty urinating.^[12]

Pharmacology

Pizotifen is a serotonin antagonist acting mainly at the 5-HT_2A and 5HT_2C receptors. It also has some activity as an antihistamine as well as some anticholinergic activity.^[13]

See also

• Benzocycloheptene
• Cyproheptadine
• Ketotifen

References

1. Stark RJ, Valenti L, Miller GC (August 2007). "Management of migraine in Australian general practice". The Medical Journal of Australia. 187 (3): 142–146. doi:10.5694/j.1326-5377.2007.tb01170.x. PMID 17680738. S2CID 10357983.
2. Jackson JL, Cogbill E, Santana-Davila R, Eldredge C, Collier W, Gradall A, et al. (2015-07-14). "A Comparative Effectiveness Meta-Analysis of Drugs for the Prophylaxis of Migraine Headache". PLOS ONE. 10 (7): e0130733. Bibcode:2015PLoSO..1030733J. doi:10.1371/journal.pone.0130733. PMC 4501738. PMID 26172390.
3. Barnes N, Millman G (July 2004). "Do pizotifen or propranolol reduce the frequency of migraine headache?". Archives of Disease in Childhood. 89 (7): 684–685. doi:10.1136/adc.2004.054668. PMC 1719986. PMID 15210509.
4. Pierangeli G, Cevoli S, Sancisi E, Grimaldi D, Zanigni S, Montagna P, Cortelli P (May 2006). "Which therapy for which patient?". Neurological Sciences. 27 (Suppl 2): S153–S158. doi:10.1007/s10072-006-0592-0. PMID 16688621. S2CID 24217802.
5. Cohen JS (November 2000). "Erythromelalgia: new theories and new therapies". Journal of the American Academy of Dermatology. 43 (5 Pt 1): 841–847. doi:10.1067/mjd.2000.109301. PMID 11050591. S2CID 40807034.
6. Standal JE (October 1977). "Pizotifen as an antidepressant". Acta Psychiatrica Scandinavica. 56 (4): 276–279. doi:10.1111/j.1600-0447.1977.tb00228.x. PMID 335788. S2CID 6445059.
7. Banki CM (March 1978). "Clinical observations with pizotifene (Sandomigran) in the treatment of nonmigrainous depressed women". Archiv für Psychiatrie und Nervenkrankheiten. 225 (1): 67–72. doi:10.1007/bf00367352. PMID 348154. S2CID 13510725.
8. Young R, Khorana N, Bondareva T, Glennon RA (October 2005). "Pizotyline effectively attenuates the stimulus effects of N-methyl-3,4-methylenedioxyamphetamine (MDMA)". Pharmacology, Biochemistry, and Behavior. 82 (2): 404–410. doi:10.1016/j.pbb.2005.09.010. PMID 16253319. S2CID 20885754.
9. Halman A, Kong G, Sarris J, Perkins D (January 2024). "Drug-drug interactions involving classic psychedelics: A systematic review". J Psychopharmacol. 38 (1): 3–18. doi:10.1177/02698811231211219. PMC 10851641. PMID 37982394.
10. 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.
11. "SANDOMIGRAN® pizotifen 500 micrograms coated tablets" (PDF). AFT Pharmaceuticals Ltd. Medsafe: New Zealand Medicines and Medical Devices Safety. 21 June 2019.
12. "Pizotifen". Universal reference book of medicines – via Likarstwo.ru.
13. Dixon AK, Hill RC, Roemer D, Scholtysik G (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. 27 (10): 1968–1979. PMID 411500.

External links

• Sandomigran drug data sheet