Cisaprid

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Achtung

• Gefahrenhinweise

  H318：Verursacht schwere Augenschäden.

• Sicherheit

  P280：Schutzhandschuhe/Schutzkleidung/Augenschutz tragen.

  P305+P351+P338：BEI KONTAKT MIT DEN AUGEN: Einige Minuten lang behutsam mit Wasser spülen. Eventuell vorhandene Kontaktlinsen nach Möglichkeit entfernen. Weiter spülen.

  P310：Sofort GIFTINFORMATIONSZENTRUM/Arzt/ anrufen.

Cisapride Chemische Eigenschaften,Einsatz,Produktion Methoden

• R-Sätze Betriebsanweisung:

  R41:Gefahr ernster Augenschäden.

• S-Sätze Betriebsanweisung:

  S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
  S39:Schutzbrille/Gesichtsschutz tragen.

• Beschreibung

  Cisapride is a gastroprokinetic useful in the treatment of reflux esophagitis, constipation, and a variety of gastro-intestinal motility disorders. Its novel mechanism of action is thought to involve the enhancement of acetylcholine release in the mysenteric plexus of the gut. It is reportedly devoid of CNS and cardiac side-effects.

• Chemische Eigenschaften

  White Solid

• Originator

  Janssen (Belgium)

• Verwenden

  Cisapride Monohydrate is a cardioactive drug that causes prolongation of cardiac repolarization in human; selective serotonin 5-HT4 receptor agonist.

• Verwenden

  Peristaltic stimulant;5-HT antagonist

• Verwenden

  A Serotonin 5-HT4 receptro agonist. Used as a Gastroprokinetic

• Verwenden

  isoflavone used as a cholagogue and cathartic

• Indications

  Cisapride (Propulsid) is serotonin-4 (5-HT4) receptor agonists that stimulate GI motility. Cisapride appears to act by facilitating the release of acetylcholine from the myenteric plexus. It has no antiadrenergic, antidopaminergic, or cholinergic side effects. Following oral administration, peak plasma levels occur in 1.5 to 2 hours; the drug’s half-life is 10 hours.

• Definition

  ChEBI: The amide resulting from formal condensation of 4-amino-5-chloro-2-methoxybenzoic acid with cis-1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidin-4-amine. It has been used (as its monohydrate or as its tartrate) for the treatment of gastro-oeso hageal reflux disease and for non-ulcer dyspepsia, but its propensity to cause cardiac arrhythmias resulted in its complete withdrawal from many countries, including the U.K., and restrictions on its use elsewhere.

• Manufacturing Process

  A mixture of 1-[3-(4-fluorophenoxy)-propyl]-3-methoxy-4-piperidinone (140 mg), benzylamine (61 mg), Pd 10% on charcoal (100 mg) and a 0.02% solution of thiophene in THF was reacted under hydrogen gas for 3 hours at 50°C. The catalyst was filtered off and fresh palladium 10% on charcoal (100 mg) was added. Debenzylation of the formed intermediate took place under hydrogen atmosphere for 18 hours at 50°C. The reaction mixture was filtered and evaporated under a stream of nitrogen to yield 1-[3-(4-fluorophenoxy)- propyl]-3-methoxy-4-piperidinamine having a cis/trans ratio of about 93/7. 1-[3-(4-Fluorophenoxy)-propyl]-3-methoxy-4-piperidinamine (50 g) was dissolved in methyl isobutylketone (250 ml) and a nitric acid solution (65%, 12.8 ml) was carefully added so that the temperature of the solution did not exceed 45°C. The reaction mixture was stirred at a temperature of 30°C and seeded. When crystallisation started, the reaction mixture was cooled to 0°C and stirred for another 2 hours. The product was filtered off, washed with a small amount of toluene and dried, yielding 1-[3-(4-fluorophenoxy)-propyl]-3- methoxy-4-piperidinamine nitrate (m.p. 60°C).
  1-[3-(4-Fluorophenoxy)-propyl]-3-methoxy-4-piperidinamine nitrate was dissolved in water (95 ml). The reaction mixture was stirred and toluene (95 ml) was added. A NaOH solution (50%, 10.3 ml) was slowly added and the temperature of the reaction mixture was raised to 75°C. After 30 min, the aqueous layer was discarded and the organic layer was evaporated, yielding 1-[3-(4-fluorophenoxy)-propyl]-3-methoxy-4-piperidinamine having a cis/trans ratio equal to or higher than 98/2.
  To a solution of 4-amino-5-chloro-2-methoxybenzoic acid (20.2 g) in methyl isobutylketone (250 ml) and triethyl amine (15.3 ml) was slowly dropped ethyl chloroformate (9.6 ml). The reaction mixture was stirred for 30 min at room temperature. To the formed mixed anhydride was then added 1-[3-(4- fluorophenoxy)-propyl]-3-methoxy-4-piperidinamine (28.2 g) and the reaction mixture was stirred for 2 hours at room temperature. Subsequently, the reaction mixture was washed with water (80 ml) and a NaOH solution (6.5% w/v, 50 ml). The organic layer was warmed to 65°C and methanol (50 ml) and water (8.5 ml) were added. The solution was cooled slowly and stirred for 2 days during which crystallisation occurred, yielding benzamide, 4-amino-5- chloro-N-(1-(3-(4-fluorophenoxy)propyl)-3-methoxy-4-piperidinyl)-2-methoxy- , monohydrate, cis- (Cisapride) having a cis/trans ratio higher than 99/1.

• Trademarks

  Propulsid (Janssen);Calmax;Cisapid;Cismotil;Digenol;Prepulsid.

• Therapeutic Function

  Gastrointestinal drug

• Biologische Aktivität

  5-HT 4 receptor agonist and gastrokinetic agent. Stimulates intestinal acetylcholine release, possibly via 5-HT 4 receptor-dependent and -independent mechanisms, leading to increased intestinal motility.

• Clinical Use

  Cisapride has been successfully used to treat gastroparesis and mild gastroesophageal reflux disease.

• Nebenwirkungen

  The most frequent side effect has been diarrhea. A few patients had seizure activity that was reversible after medication was discontinued. Cisapride was pulled from the U. S. market after deaths from drug-associated cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation, torsades de pointes, and QT prolongation.

• Veterinary Drugs and Treatments

  Proposed uses for cisapride in small animals includes esophageal reflux and treatment of primary gastric stasis disorders. Cisapride has been found to be useful in the treatment of constipation and megacolon in cats.

• Stoffwechselwegen

  Cisapride 14C labeled at the carbonyl carbon and 3H labeled at the fluorophenyl moiety or at the piperidine ring is investigated using some animals. N- Dealkylation at the nitrogen of the piperidine ring, resulting in the main urinary metabolite norcisapride, and aromatic hydroxylation of the fluorinated phenyl ring are the major metabolic pathways in dogs and humans. Norcisapride excretion accounts for 14% of the dose in dogs and 41-45% in humans. Minor metabolic pathways are O-dearylation of the 4- fluorophenyl group and oxidation on the piperidine ring (rat, rabbits and dogs: Lavrijsen et al. (1986)15).

• Lager

  Store at RT

Cisapride Upstream-Materialien And Downstream Produkte

Cisaprid Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

Global(261)Suppliers

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