Pizotifen

Pizotifen

Systematic (IUPAC) name
4-(1-methyl-4-piperidylidine)-9,10-dihydro -4H-benzo-[4,5]cyclohepta[1,2]-thiophene
Clinical data
Trade names	Sandomigran
AHFS/Drugs.com
Pregnancy category	AU: B1
Legal status	AU: Prescription Only (S4) CA: ℞-only UK: Prescription-only (POM)
Routes of administration	Oral
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
Biological half-life	23 hours
Excretion	18% feces, 55% urine (both as metabolites).
Identifiers
CAS Registry Number	N
ATC code	N02
PubChem	CID:
IUPHAR/BPS
ChemSpider	Y
UNII	Y
KEGG	Y
ChEMBL	Y
Chemical data
Formula	C19H21NS
Molecular mass	295.443 g/mol
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
N

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

Uses

The main medical use for pizotifen is for the prevention of vascular headache including migraine and cluster headache. Pizotifen is one of a range of medications used for this purpose, other options include propranolol, topiramate, valproic acid and amitriptyline. While pizotifen is reasonably effective,^[2] 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.^[3] 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. ^[4]

Other applications for which pizotifen may be used include as an antidepressant, or for the treatment of anxiety or social phobia.^[5][6] Animal studies also suggest that pizotyline could be used in the treatment of serotonin syndrome or MDMA overdose^[7] in a similar manner to the closely related antihistamine/antiserotonin drug cyproheptadine.

Adverse effects

Side effects include sedation, dry mouth, drowsiness, increased appetite and weight gain.^[8] 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 drug exhibits a relatively small anticholinergic effect. Dose adjustment is required in patients having renal insufficiency. Hepatic injury has also been reported. Pizotifen treatment should be discontinued if there is any clinical evidence of hepatic 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.^[9] 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.^[10]

Mechanism of Action

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.^[11]

See also

• Benzocycloheptene
• Cyproheptadine

References

External links

• Sandomigran drug data sheet