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Details

Stereochemistry ACHIRAL
Molecular Formula C19H21NS.C4H4O4
Molecular Weight 411.514
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of PIZOTYLINE MALEATE

SMILES

OC(=O)\C=C/C(O)=O.CN1CCC(CC1)=C2C3=C(CCC4=C2C=CC=C4)SC=C3

InChI

InChIKey=GGYSHFFKUHGBIK-BTJKTKAUSA-N
InChI=1S/C19H21NS.C4H4O4/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;5-3(6)1-2-4(7)8/h2-5,10,13H,6-9,11-12H2,1H3;1-2H,(H,5,6)(H,7,8)/b;2-1-

HIDE SMILES / InChI

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

Molecular Formula C4H4O4
Molecular Weight 116.0722
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Description

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

TargetsConditions

Conditions

PubMed

PubMed

TitleDatePubMed
Comparative trial of serotonin antagonists in the management of migraine.
1970 May 9
Effects of chronic treatment with antidepressants on aggressiveness induced by clonidine in mice.
1982
The role of the central serotonergic system in pilocarpine-induced seizures: receptor mechanisms.
1989 Nov
Agonist activity of antimigraine drugs at recombinant human 5-HT1A receptors: potential implications for prophylactic and acute therapy.
1997 Jun
French guidelines for the diagnosis and management of migraine in adults and children.
2004 Aug
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 Dec 28
Topiramate in migraine prevention: evidence-based medicine from clinical trials.
2004 Oct
Raynaud phenomena and migraine in two children: inclusion within a family of related disorders.
2005 Dec
Cyclic Vomiting Syndrome in 41 adults: the illness, the patients, and problems of management.
2005 Dec 21
Use of intravenous midazolam and clonidine in cyclical vomiting syndrome: a case report.
2005 Jan
Stability studies on some benzocycloheptane antihistaminic agents.
2005 Jan 4
Serotonin2C receptor blockade and thermoregulation during exercise in the heat.
2005 Mar
Anticipatory nausea in cyclical vomiting.
2005 Mar 24
Pizotyline effectively attenuates the stimulus effects of N-methyl-3,4-methylenedioxyamphetamine (MDMA).
2005 Oct
Weight variations in the prophylactic therapy of primary headaches: 6-month follow-up.
2005 Sep
Topiramate for migraine prophylaxis.
2006 Aug
The Effect of Paroxetine on the Reduction of Migraine Frequency is Independent of Its Anxiolytic Effect.
2006 Dec
Adult abdominal migraine: a new syndrome or sporadic feature of migraine headache? A case report.
2006 Jan
Potential vascular alpha1-adrenoceptor blocking properties of an array of 5-HT receptor ligands in the rat.
2006 Mar 27
Which therapy for which patient?
2006 May
Evaluation of guided imagery as treatment for recurrent abdominal pain in children: a randomized controlled trial.
2006 Nov 8
Pharmacological prevention of migraine: to be considered case by case.
2006 Oct
Anatomical alterations of the visual motion processing network in migraine with and without aura.
2006 Oct
Topiramate in the prevention of migraine: a review of its efficacy, tolerability, and acceptability.
2006 Sep
Recommendations for the management of migraine in paediatric patients.
2007 Apr
Management of migraine in Australian general practice.
2007 Aug 6
Pediatric migraine: pharmacologic agents for prophylaxis.
2007 Jul
[Confusional syndrome caused by pizotifen].
2007 May-Jun
Migraine associated vertigo.
2007 Sep
Stages of motor output reorganization after hemispheric stroke suggested by longitudinal studies of cortical physiology.
2008 Aug
Prophylaxis of migraine: general principles and patient acceptance.
2008 Dec
Cluster headache.
2008 Feb 15
Update on the prophylaxis of migraine.
2008 Jan
Pharmacological interventions for recurrent abdominal pain (RAP) and irritable bowel syndrome (IBS) in childhood.
2008 Jan 23
Weight gain with pizotifen therapy.
2008 Jul
Cluster headache.
2008 Jul 23
Drug use in children: cohort study in three European countries.
2008 Nov 24
Optimizing prophylactic treatment of migraine: Subtypes and patient matching.
2008 Oct
What happens to new-onset headache in children that present to primary care? A case-cohort study using electronic primary care records.
2009 Dec
Treatment of primary headache in children: a multicenter hospital-based study in France.
2009 Dec
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 Dec 30
Migraine headache in children.
2009 Jan 13
5-Hydroxytryptamine Receptor Subtypes and their Modulators with Therapeutic Potentials.
2009 Jun
Recent concepts on cyclic vomiting syndrome in children.
2010 Apr
Prophylaxis of migraine headache.
2010 Apr 20
New methods for diagnosis and treatment of vestibular diseases.
2010 Aug 9
Fulminant hepatitis possibly related to pizotifen therapy.
2010 Jul-Aug
P3MC: a double blind parallel group randomised placebo controlled trial of Propranolol and Pizotifen in preventing migraine in children.
2010 Jun 16
Prescribing for migraine with the focus on selective 5HT1-receptor agonists: a pharmacy database analysis.
2010 May
Validation and application of reversed phase high-performance liquid chromatographic method for quantification of pizotifen malate in pharmaceutical solid dosage formulations.
2010 Oct
Patents

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 Tue Oct 22 00:37:55 UTC 2019
Edited
by admin
on Tue Oct 22 00:37:55 UTC 2019
Record UNII
2S5E7G70SZ
Record Status Validated (UNII)
Record Version
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Name Type Language
PIZOTYLINE MALEATE
Common Name English
PIZOTIFEN MALEATE [WHO-DD]
Common Name English
PIZOTIFEN HYDROGEN MALEATE
Common Name English
PIPERIDINE, 4-(9,10-DIHYDRO-4H-BENZO(4,5)CYCLOHEPTA(1,2-B)THIEN-4-YLIDENE)-1-METHYL-, (Z)-2-BUTENEDIOATE (1:1)
Systematic Name English
PIZOTIFEN MALEATE
WHO-DD  
Common Name English
PIPERIDINE, 4-(9,10-DIHYDRO-4H-BENZO(4,5)CYCLOHEPTA(1,2-B)THIEN-4-YLIDENE)-1-METHYL-, (2Z)-2-BUTENEDIOATE (1:1)
Systematic Name English
Code System Code Type Description
ECHA (EC/EINECS)
246-204-5
Created by admin on Tue Oct 22 00:37:55 UTC 2019 , Edited by admin on Tue Oct 22 00:37:55 UTC 2019
PRIMARY
PUBCHEM
6439699
Created by admin on Tue Oct 22 00:37:55 UTC 2019 , Edited by admin on Tue Oct 22 00:37:55 UTC 2019
PRIMARY
CAS
24359-22-6
Created by admin on Tue Oct 22 00:37:55 UTC 2019 , Edited by admin on Tue Oct 22 00:37:55 UTC 2019
PRIMARY
EVMPD
SUB03887MIG
Created by admin on Tue Oct 22 00:37:55 UTC 2019 , Edited by admin on Tue Oct 22 00:37:55 UTC 2019
PRIMARY
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