シサプリド 化学特性,用途語,生産方法
外観
白色～わずかにうすい褐色、結晶性粉末～粉末
効能
消化管運動改善薬, セロトニン受容体作動薬
説明
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.
化学的特性
White Solid
使用
Cisapride Monohydrate is a cardioactive drug that causes prolongation of cardiac repolarization in human; selective serotonin 5-HT4 receptor agonist.
適応症
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.
定義
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.
生物活性
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.
臨床応用
Cisapride has been successfully used to treat
gastroparesis and mild gastroesophageal reflux disease.
副作用
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.
代謝経路
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).
シサプリド 上流と下流の製品情報
原材料
準備製品