Pizotifen

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Warnung

• Gefahrenhinweise

  H302：Gesundheitsschädlich bei Verschlucken.

  H361：Kann vermutlich die Fruchtbarkeit beeinträchtigen oder das Kind im Mutterleib schädigen.

• Sicherheit

  P201：Vor Gebrauch besondere Anweisungen einholen.

  P308+P313：BEI Exposition oder falls betroffen: Ärztlichen Rat einholen/ärztliche Hilfe hinzuziehen.

Pizotifen Chemische Eigenschaften,Einsatz,Produktion Methoden

• R-Sätze Betriebsanweisung:

  R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.

• S-Sätze Betriebsanweisung:

  S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
  S37/39:Bei der Arbeit geeignete Schutzhandschuhe und Schutzbrille/Gesichtsschutz tragen.

• Chemische Eigenschaften

  White to Off-White Solid

• Originator

  Sandomigran ,Sandoz ,Italy ,1972

• Verwenden

  benzocycloheptane based drug

• Verwenden

  Serotonin antagonist structurally related to Cyproheptadine. Antimigraine; appetite stimulant.

• Indications

  Pizotifen, a potent antihistamine and antiserotonin agent usually prescribed for migraine prophylaxis, has had reported success in patients with polycythemia vera.

• Definition

  ChEBI: A benzocycloheptathiophene that is 9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophene 4-ylidene)-1-methylpiperidine which is joined from the 4 position to the 4 position of an N-methylpiperidine moiety b a double bond. It is a sedating antihistamine, with strong serotonin antagonist and weak antimuscarinic activity. It is generally used as the malate salt for the treatment of migraine and the prevention of headache attacks during cluster periods.

• Manufacturing Process

  (A) Preparation of Thenylidene-(2)-Phthalide: 24.2 g of thienyl-(2)-acetic acid, 52.0 g of phthalic acid anhydride, 4.0 g of anhydrous sodium acetate and 125 ml of 1-methylpyrrolidone-(2) are heated while stirring in an open flask for 3 hours to 205° to 208°C, while nitrogen is passed through. It is then cooled and the viscous reaction mixture poured into 1 liter of water. The precipitated substance is filtered off, washed with water and then dissolved in 200 ml of chloroform. After filtering off some undissolved substance, shaking is effected twice with 100 ml of 2 N sodium carbonate solution and then with water, drying is then carried out over sodium sulfate and the volume is reduced by evaporation. The crude phthalide is repeatedly recrystallized from ethanol, while treating with animal charcoal. It melts at 114° to 115°C.
  (B) Preparation of o-[2-Thienyl-(2')-Ethyl]Benzoic Acid: 24.0 g of thenylidene(2)-phthalide, 8.8 g of red pulverized phosphorus, 240 ml of hydrochloric acid (d = 1.7) and 240 ml of glacial acetic acid are heated to boiling under nitrogen and while stirring vigorously. 70 ml toluene are then added and 6.0 g of red phosphorus added in small portions over a period of 1 hour. It is then poured into 3 liters of ice water, stirred with 300 ml of chloroform and the phosphorus removed by filtration.
  The chloroform phase is then removed, the aqueous phase extracted twice more with 200 ml of chloroform and the united extracts shaken out 4 times,each time with 200 ml of 2 N sodium hydroxide solution. The alkaline solution is then rendered acid to Congo red reagent, using hydrochloric acid and extracted 3 times with chloroform. After drying over sodium sulfate and evaporating the solvent, the residue is chromatographed on aluminum oxide (Activity Stage V). The substance eluted with benzene and benzene/chloroform (1:1) is recrystallized from chloroform/hexane (1:1); MP 107° to 109°C.
  (C) Preparation of 9,10-Dihydro-4H-Benzo[4,5]Cyclohepta[1,2-b]Thiophen(4)-One: 200 ml of 85% phosphoric acid and 112 g of phosphorus pentoxide are heated to 135°C. 7.0 g of o-[2-thienyl-(2')-ethyl]benzoic acid are then introduced while stirring thoroughly over a period of 30 min. Stirring is then continued for another hour at 135°C and the reaction mixture is then stirred into 1 liter of ice water. Extraction is then effected 3 times, using 250 ml ether portions, the ethereal extract is washed with 2 N sodium carbonate solution, dried over sodium sulfate and reduced in volume by evaporation. The residue is boiled up with 55 ml of ethanol, the solution freed of resin by decanting and then stirred at room temperature for 6 hours with animal charcoal. It is then filtered off, reduced in volume in a vacuum and the residue distilled. BP 120° to 124°C/0.005 mm, nD24.5 = 1.6559.
  (D) Preparation of 4-[1'-Methyl-Piperidyl-(4')]-9,10-Dihydro-4HBenzo[4,5]Cyclohepta[1,2b]Thiophen-(4)-ol: 0.94 g of magnesium filings which have been activated with iodine are covered with a layer of absolute tetrahydrofuran and etched with a few drops of ethylene bromide. A solution of 5.0 g of 1-methyl-4-chloropiperidine in 5 ml of tetrahydrofuran is then added dropwise and boiling then effected for a further hour under reflux. After cooling to room temperature, the solution of 4.5 g of 9,10-dihydro-4Hbenzo[4,5]cyclohepta[1,2-b]thiophen-(4)-one in 5 ml of tetrahydrofuran is added dropwise.
  Stirring is carried out first for 3 hours at room temperature and then for 2 hours at boiling temperature, it is then cooled and poured into 300 ml of icecold 20% ammonium chloride solution. It is then shaken out with methylene chloride, the methylene chloride solution washed with water and shaken 3 times with 30 ml portions of aqueous 2 N tartaric acid solution. The tartaric acid extract is rendered alkaline while cooling thoroughly and then extracted twice with methylene chloride. After washing with water, drying over potassium carbonate and reducing in volume b

• Trademarks

  Sandomigran (Novartis).

• Therapeutic Function

  Migraine therapy

• Biochem/physiol Actions

  Pizotifen is a serotonin antagonist acting mainly at the 5-HT1, 5-HT2A and 5HT2C receptors with some antihistamine activity. It is used for the prevention of vascular headache including migraine and cluster headache.

• Clinical Use

  Prophylactic treatment of vascular headaches including migraine

• Arzneimittelwechselwirkung

  Potentially hazardous interactions with other drugs
  Adrenergic neurone blockers: pizotifen antagonises hypotensive effect.

• Stoffwechsel

  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.

Pizotifen Upstream-Materialien And Downstream Produkte

Pizotifen Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

Global(209)Suppliers

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