PIZOTYLINE

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H21NS
Molecular Weight	295.442
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1CCC(CC1)=C2C3=C(CCC4=CC=CC=C24)SC=C3

InChI

InChIKey=FIADGNVRKBPQEU-UHFFFAOYSA-N

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

HIDE SMILES / InChI

Molecular Formula	C19H21NS
Molecular Weight	295.442
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.medicines.org.uk/emc/medicine/24179
Curator's Comment: description was created based on several sources, including https://www.drugs.com/uk/sanomigran-1-5mg-tablets-leaflet.html | https://www.drugs.com/uk/pizotifen-0-5mg-tablets-leaflet.html | https://www.ncbi.nlm.nih.gov/pubmed/24189186

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. Pizotifen is a serotonin antagonist acting mainly at the 5-HT2A and 5HT2C receptors. It also has some activity as an antihistamine as well as some anticholinergic activity. 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, 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. 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. 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. Pizotifen is well absorbed from the gastro-intestinal tract, peak plasma concentrations occurring approximately 5 hours after oral administration. The absorption of pizotifen is fast (absorption half life 0.5 to 0.8 hours) and nearly complete (80%). Over 90% is bound to plasma proteins. Pizotifen undergoes extensive metabolism. Over half of a dose is excreted in the urine, chiefly as metabolites; a significant proportion is excreted in the faeces. The primary metabolite of pizotifen (N-glucuronide conjugate) has a long elimination half-life of about 23 hours.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serotonin 2b (5-HT2b) receptor 60 Target ID: CHEMBL1833 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24189186	Antagonist 2849	2.0 nM [Ki]
Serotonin 2c (5-HT2c) receptor 131 Target ID: CHEMBL225 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24189186	Antagonist 2849	1.4 nM [Ki]
Serotonin 2a (5-HT2a) receptor 237 Target ID: CHEMBL224 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24189186	Antagonist 2849	7.5 nM [Ki]
Serotonin 7 (5-HT7) receptor 30 Target ID: CHEMBL3155 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24189186	Antagonist 2849	25.0 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Cluster headache 10 Sources: https://www.medicines.org.uk/emc/medicine/24179	Primary	Approved 8583	Sandomigran Approved Use Unknown
Common migraine 4 Sources: https://www.medicines.org.uk/emc/medicine/24179	Primary	Approved 8583	Sandomigran Approved Use Unknown
Classical migraine 4 Sources: https://www.medicines.org.uk/emc/medicine/24179	Primary	Approved 8583	Sandomigran Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
5 ng/mL DRUG LABEL https://www.medicines.org.uk/emc/product/5917/smpc#gref	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:		PIZOTYLINE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN
14 ng/mL DRUG LABEL https://www.medicines.org.uk/emc/product/5917/smpc#gref	1 mg 3 times / day steady-state, oral dose: 1 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		PIZOTYLINE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
23 h DRUG LABEL https://www.medicines.org.uk/emc/product/5917/smpc#gref	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:		PIZOTYLINE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
9% DRUG LABEL https://www.medicines.org.uk/emc/product/5917/smpc#gref	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:		PIZOTYLINE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
0.5 mg 3 times / day multiple, oral Studied dose Dose: 0.5 mg, 3 times / day Route: oral Route: multiple Dose: 0.5 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2074163/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2074163/	Disc. AE: Weight gain, Sleepiness... AEs leading to discontinuation/dose reduction: Weight gain Sleepiness Sources: https://pubmed.ncbi.nlm.nih.gov/2074163/
1 mg 3 times / day multiple, oral Studied dose Dose: 1 mg, 3 times / day Route: oral Route: multiple Dose: 1 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1095308/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/1095308/	Disc. AE: Weight gain, Depression... AEs leading to discontinuation/dose reduction: Weight gain (11.1%) Depression (7.4%) Hunger abnormal (3.7%) Confusion (3.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/1095308/

AEs

AE	Significance	Dose	Population
Sleepiness	Disc. AE	0.5 mg 3 times / day multiple, oral Studied dose Dose: 0.5 mg, 3 times / day Route: oral Route: multiple Dose: 0.5 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2074163/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2074163/
Weight gain	Disc. AE	0.5 mg 3 times / day multiple, oral Studied dose Dose: 0.5 mg, 3 times / day Route: oral Route: multiple Dose: 0.5 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2074163/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2074163/
Weight gain	11.1% Disc. AE	1 mg 3 times / day multiple, oral Studied dose Dose: 1 mg, 3 times / day Route: oral Route: multiple Dose: 1 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1095308/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/1095308/
Confusion	3.7% Disc. AE	1 mg 3 times / day multiple, oral Studied dose Dose: 1 mg, 3 times / day Route: oral Route: multiple Dose: 1 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1095308/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/1095308/
Hunger abnormal	3.7% Disc. AE	1 mg 3 times / day multiple, oral Studied dose Dose: 1 mg, 3 times / day Route: oral Route: multiple Dose: 1 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1095308/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/1095308/
Depression	7.4% Disc. AE	1 mg 3 times / day multiple, oral Studied dose Dose: 1 mg, 3 times / day Route: oral Route: multiple Dose: 1 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1095308/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/1095308/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087 inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 2057 CYP1A2 2153 CYP19A1 429	P-gp 2052 UGT1A3 470 UGT1A4 399 UGT2B10 131

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE1MTI3OTYifX0=	no [IC50 >10 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzk3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE1MTI3OTYifX0=	no [IC50 >10 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTUxMjc5NiJ9fQ==	no [IC50 >10 uM]
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/27400#section=BioAssay-Results Page: 102.0	no
CYP3A4 2633	inducer 1966 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/27400#section=BioAssay-Results Page: 26.0	yes [Activation 28.1838 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyODkiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTUxMjc5NiJ9fQ==	yes [IC50 1.2589 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE1MTI3OTYifX0=	yes [IC50 3.9811 uM]

Drug as victim

Target	Modality	Activity
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/27400#section=BioAssay-Results Page: 16 \| 146	inconclusive
UGT1A3 470	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23611809/	yes
UGT1A4 399	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23611809/	yes
UGT2B10 131	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23611809/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/27400#section=BioAssay-Results Page: 11.0

PubMed

Title	Date	PubMed
Effects of chronic treatment with antidepressants on aggressiveness induced by clonidine in mice.	1982	6813425
Arterial complications of migraine treatment with methysergide and parenteral ergotamine.	1982 Jul 24	6807440
Agonist activity of antimigraine drugs at recombinant human 5-HT1A receptors: potential implications for prophylactic and acute therapy.	1997 Jun	9205951
Solubility of solid dispersions of pizotifen malate and povidone.	2001 Jul	11548858
[Effectiveness of tolfenamic acid in the prevention of migraine].	2002	12474702
Central pathways for cough in man--unanswered questions.	2002	12099782
Pharmacological interventions for recurrent abdominal pain (RAP) in childhood.	2002	11869650
Abdominal migraine: evidence for existence and treatment options.	2002	11817981
Cluster headache: aetiology, diagnosis and management.	2002	11790156
Cyclic vomiting syndrome in Thai children.	2002 Aug	12403255
Paroxysmal hemicrania and cluster headache: two discrete entities or is there an overlap?	2002 Dec	12472514
[Critical ischaemia of the limbs and localized livedo in a case of ergotism].	2002 Jan 25	11807658
Migraine and Raynaud phenomenon: possible late complications of Kawasaki disease.	2002 Mar	11903548
Hypotension caused by extracorporeal circulation: serotonin from pump-activated platelets triggers nitric oxide release.	2002 Nov 12	12427656
[Current views on migraine and anti-migraine preparations].	2003	14598505
Systematic review of treatments for recurrent abdominal pain.	2003 Jan	12509588
French guidelines for the diagnosis and management of migraine in adults and children.	2004 Aug	15476911
Determination of ketotifen in human plasma by LC-MS.	2004 Jan 27	14738922
Do pizotifen or propranolol reduce the frequency of migraine headache?	2004 Jul	15210509
Topiramate in migraine prevention: evidence-based medicine from clinical trials.	2004 Oct	15549548
Raynaud phenomena and migraine in two children: inclusion within a family of related disorders.	2005 Dec	16421056
Cyclic Vomiting Syndrome in 41 adults: the illness, the patients, and problems of management.	2005 Dec 21	16368014
Stability studies on some benzocycloheptane antihistaminic agents.	2005 Jan 4	15620527
Serotonin2C receptor blockade and thermoregulation during exercise in the heat.	2005 Mar	15741836
Pizotyline effectively attenuates the stimulus effects of N-methyl-3,4-methylenedioxyamphetamine (MDMA).	2005 Oct	16253319
Weight variations in the prophylactic therapy of primary headaches: 6-month follow-up.	2005 Sep	16362700
The Effect of Paroxetine on the Reduction of Migraine Frequency is Independent of Its Anxiolytic Effect.	2006 Dec	20396527
Evaluation of guided imagery as treatment for recurrent abdominal pain in children: a randomized controlled trial.	2006 Nov 8	17090333
Cluster headache.	2008 Feb 15	19450329
Pharmacological interventions for recurrent abdominal pain (RAP) and irritable bowel syndrome (IBS) in childhood.	2008 Jan 23	18254013
Prophylaxis of migraine headache.	2010 Apr 20	20159899
Fulminant hepatitis possibly related to pizotifen therapy.	2010 Jul-Aug	20571104
Prescribing for migraine with the focus on selective 5HT1-receptor agonists: a pharmacy database analysis.	2010 May	20420788

Patents

Sample Use Guides

In Vivo Use Guide

1.5mg daily (one 1.5mg tablet at night or 0.5mg tablets three times daily).

Route of Administration: Oral

In Vitro Use Guide

HEK293-EBNA cell was used as the gene transferring cell. Cultured HEK293-EBNA cells expressing human 5-HT2B receptor were washed with PBS(-). The cells were scraped in the presence of PBS(-), and the cells were recovered by centrifugation (1000 rpm, 10 min, 4 OC). They were homogenized using Polytron (PTA 10-TS) in the presence of 5 mM Tris-HCl (pH 7.4) buffer and centrifuged (40,000 xg. 10 min, 4 OC). They were suspended using a homogenizer in the presence of 50 mM Tris–HCl (pH 7.4) buffer. They were subjected to centrifugation (40,000 xg, 10 min, 4 OC), suspended in 50 mM Tris–HCl (pH 7.4) and stored at 80 0C. A total volume of 500 mkL containing 50 mM Tris–HCl–4 mM CaCl2 (pH 7.4) buffer, the human 5-HT2B receptor expressing HEK293-EBNA cell membrane preparation and a radio ligand [3H] Mesulergine (3.1 TBq/mmol) was incubated at 25 OC for 1 h. The Pizotifen was dissolved in 100% DMSO and diluted to respective concentrations.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:40:14 GMT 2025` Edited by `admin` on `Mon Mar 31 18:40:14 GMT 2025`
Record UNII	0BY8440V3N
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PIZOTYLINE

Official Name

English

PIZOTIFEN

Preferred Name

English

PIZOTIFEN [MART.]

Common Name

English

BC-105

Code

English

Pizotifen [WHO-DD]

Common Name

English

PIZOTYLINE [USAN]

Common Name

English

PIZOTYLINE [MI]

Common Name

English

SANDOMIGRAN

Brand Name

English

PIPERIDINE, 4-(9,10-DIHYDRO-4H-BENZO(4,5)CYCLOHEPTA(1,2-B)THIEN-4-YLIDENE)-1-METHYL-

Systematic Name

English

4-(9,10-Dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thien-4-ylidene)-1-methylpiperidine

Systematic Name

English

pizotifen [INN]

Common Name

English

Classification Tree Code System Code

WHO-ATC

N02CX01