Pizotifen

Pizotifen
	File:Pizotifen.svg
Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy; category	AU: B1 ; ;
Routes of; administration	Oral
ATC code	N02CX01 (WHO) ;
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	23h
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 ;
PubChem CID	27400;
IUPHAR/BPS	93;
ChemSpider	25497 ;
UNII	0BY8440V3N;
KEGG	D05523 ;
ChEMBL	ChEMBL294951 ;
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
Formula	C19H21NS
Molar mass	295.443 g/mol
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 ; Key:FIADGNVRKBPQEU-UHFFFAOYSA-N ;
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Template:Pizotifen Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Pratik Bahekar, MBBS [2]

For patient information about Pizotifen, click here

Overview

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]

Mechanism

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.^[2]

Side effects

Side effects include sedation, dry mouth, drowsiness, increased appetite and weight gain.^[3] Occasionally it may cause nausea or dizziness. In rare cases, anxiety, aggression and depression may also occur. Rare side effects include confusion, stomach pain, vision changes, mood changes,and sexual dysfunction.

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.^[4] 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.^[5]

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 propanolol, valproic acid and amitryptyline. While pizotifen is reasonably effective,^[6] 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.^[7] It is not effective in relieving migraine attacks once in progress.

Other applications for which pizotifen may be used include as an antidepressant, or for the treatment of anxiety or social phobia.^[8]^[9] Animal studies also suggest that pizotyline could be used in the treatment of serotonin syndrome or MDMA overdose^[10] in a similar manner to the closely related antihistamine/antiserotonin drug cyproheptadine.

Dose

Typically adult does is 1.5mg at night or 500 micrograms 3 times daily, adjusted according to response. Max single does 3mg, max daily dose 4.5mg.

Child over 2 years and up, up to 1.5mg daily in divided dose; max single dose at night 1mg.

Sandomigran drug data sheet

References

↑ Stark RJ, Valenti L, Miller GC. Management of migraine in Australian general practice. Medical Journal of Australia. 2007 Aug 6;187(3):142-6.
↑ 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). Arzneimittelforschung. 1977;27(10):1968-79.
↑ 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.
↑ "Emedicine".
↑ "Likarstwo.ru".
↑ Barnes N, Millman G. Do pizotifen or propranolol reduce the frequency of migraine headache? Archives of Disease in Childhood. 2004 Jul;89(7):684-5.
↑ Pierangeli G, Cevoli S, Sancisi E, Grimaldi D, Zanigni S, Montagna P, Cortelli P. Which therapy for which patient? Neurological Sciences. 2006 May;27 Suppl 2:S153-8.
↑ Standal JE. Pizotifen as an antidepressant. Acta Psychiatrica Scandinavica. 1977 Oct;56(4):276-9.
↑ Banki CM. Clinical observations with pizotifene (Sandomigran) in the treatment of nonmigrainous depressed women. Archiv fur Psychiatrie und Nervenkrankheiten. 1978 Mar 7;225(1):67-72.
↑ 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. 2005 Oct;82(2):404-10.

Template:Pharma-stub Template:Antimigraine preparations

[1] Stark RJ, Valenti L, Miller GC. Management of migraine in Australian general practice. Medical Journal of Australia. 2007 Aug 6;187(3):142-6.

[2] 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). Arzneimittelforschung. 1977;27(10):1968-79.

[3] 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.

[4] "Emedicine".

[5] "Likarstwo.ru".

[6] Barnes N, Millman G. Do pizotifen or propranolol reduce the frequency of migraine headache? Archives of Disease in Childhood. 2004 Jul;89(7):684-5.

[7] Pierangeli G, Cevoli S, Sancisi E, Grimaldi D, Zanigni S, Montagna P, Cortelli P. Which therapy for which patient? Neurological Sciences. 2006 May;27 Suppl 2:S153-8.

[8] Standal JE. Pizotifen as an antidepressant. Acta Psychiatrica Scandinavica. 1977 Oct;56(4):276-9.

[9] Banki CM. Clinical observations with pizotifene (Sandomigran) in the treatment of nonmigrainous depressed women. Archiv fur Psychiatrie und Nervenkrankheiten. 1978 Mar 7;225(1):67-72.

[10] 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. 2005 Oct;82(2):404-10.

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