PIZOTIFEN HYDROCHLORIDE

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H21NS.ClH
Molecular Weight	331.903
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=INPORWDLYCTBBN-UHFFFAOYSA-N

InChI=1S/C19H21NS.ClH/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;1H

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

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

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
Validation and application of reversed phase high-performance liquid chromatographic method for quantification of pizotifen malate in pharmaceutical solid dosage formulations.	2010-10	20884459
New methods for diagnosis and treatment of vestibular diseases.	2010-08-09	21173877
Fulminant hepatitis possibly related to pizotifen therapy.	2010-06-24	20571104
P3MC: a double blind parallel group randomised placebo controlled trial of Propranolol and Pizotifen in preventing migraine in children.	2010-06-16	20553601
Prescribing for migraine with the focus on selective 5HT1-receptor agonists: a pharmacy database analysis.	2010-05	20420788
Prophylaxis of migraine headache.	2010-04-20	20159899
Recent concepts on cyclic vomiting syndrome in children.	2010-04	20535344
Cluster headache.	2010-02-09	21718584
Potential contribution of prescription practices to the emergence and spread of chloroquine resistance in south-west Nigeria: caution in the use of artemisinin combination therapy.	2009-12-30	20042098
What happens to new-onset headache in children that present to primary care? A case-cohort study using electronic primary care records.	2009-12	19911465
Treatment of primary headache in children: a multicenter hospital-based study in France.	2009-12	19771388
5-Hydroxytryptamine Receptor Subtypes and their Modulators with Therapeutic Potentials.	2009-06	22505971
Migraine headache in children.	2009-01-13	19445776
Prophylaxis of migraine: general principles and patient acceptance.	2008-12	19337456
Drug use in children: cohort study in three European countries.	2008-11-24	19029175
Optimizing prophylactic treatment of migraine: Subtypes and patient matching.	2008-10	19209286
Stages of motor output reorganization after hemispheric stroke suggested by longitudinal studies of cortical physiology.	2008-08	18234688
Cluster headache.	2008-07-23	18651939
Weight gain with pizotifen therapy.	2008-07	18381348
Pizotifen relieves acute migraine symptoms.	2008-03-01	21516161
Cluster headache.	2008-02-15	19450329
Pharmacological interventions for recurrent abdominal pain (RAP) and irritable bowel syndrome (IBS) in childhood.	2008-01-23	18254013
Update on the prophylaxis of migraine.	2008-01	18325296
[Confusional syndrome caused by pizotifen].	2007-10-19	17941762
Migraine associated vertigo.	2007-09	19513278
Management of migraine in Australian general practice.	2007-08-06	17680738
Pediatric migraine: pharmacologic agents for prophylaxis.	2007-07	17550953
Recommendations for the management of migraine in paediatric patients.	2007-04	17425470
The Effect of Paroxetine on the Reduction of Migraine Frequency is Independent of Its Anxiolytic Effect.	2006-12	20396527
Evaluation of guided imagery as treatment for recurrent abdominal pain in children: a randomized controlled trial.	2006-11-08	17090333
Pharmacological prevention of migraine: to be considered case by case.	2006-10	17128528
Anatomical alterations of the visual motion processing network in migraine with and without aura.	2006-10	17048979
Topiramate in the prevention of migraine: a review of its efficacy, tolerability, and acceptability.	2006-09	19412473
Topiramate for migraine prophylaxis.	2006-08	16903488
Which therapy for which patient?	2006-05	16688621
Potential vascular alpha1-adrenoceptor blocking properties of an array of 5-HT receptor ligands in the rat.	2006-03-27	16545797
Adult abdominal migraine: a new syndrome or sporadic feature of migraine headache? A case report.	2006-01	16420398
Cyclic Vomiting Syndrome in 41 adults: the illness, the patients, and problems of management.	2005-12-21	16368014
Raynaud phenomena and migraine in two children: inclusion within a family of related disorders.	2005-12	16421056
Pizotyline effectively attenuates the stimulus effects of N-methyl-3,4-methylenedioxyamphetamine (MDMA).	2005-10	16253319
Weight variations in the prophylactic therapy of primary headaches: 6-month follow-up.	2005-09	16362700
Anticipatory nausea in cyclical vomiting.	2005-03-24	15790392
Serotonin2C receptor blockade and thermoregulation during exercise in the heat.	2005-03	15741836
Use of intravenous midazolam and clonidine in cyclical vomiting syndrome: a case report.	2005-01	15649168
Practice parameter: pharmacological treatment of migraine headache in children and adolescents: report of the American Academy of Neurology Quality Standards Subcommittee and the Practice Committee of the Child Neurology Society.	2004-12-28	15623677
Agonist activity of antimigraine drugs at recombinant human 5-HT1A receptors: potential implications for prophylactic and acute therapy.	1997-06	9205951
The role of the central serotonergic system in pilocarpine-induced seizures: receptor mechanisms.	1989-11	2533336
Arterial complications of migraine treatment with methysergide and parenteral ergotamine.	1982-07-24	6807440
Effects of chronic treatment with antidepressants on aggressiveness induced by clonidine in mice.	1982	6813425
Comparative trial of serotonin antagonists in the management of migraine.	1970-05-09	4393372

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 20:49:57 GMT 2025` Edited by `admin` on `Mon Mar 31 20:49:57 GMT 2025`
Record UNII	MKZ19G896I
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PIZOTYLINE HYDROCHLORIDE

Preferred Name

English

PIZOTIFEN HYDROCHLORIDE

Common Name

English

Pizotifen hydrochloride [WHO-DD]

Common Name

English

PIZOTYLINE HYDROCHLORIDE [MI]

Common Name

English

NSC-291564

Code

English

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

Systematic Name

English

Code System Code Type Description

EVMPD

SUB03886MIG