プルカロプリド 化学特性,用途語,生産方法
効能
消化管運動改善薬, セロトニン受容体作動薬
説明
Prucalopride is a potent and selective agonist of the serotonin (5-HT) receptor subtype 5-HT
4 (K
is = 2.5 and 8 nM for human 5-HT
4A and 5-HT
4B, respectively). Prucalopride is greater than 250-fold selective for 5-HT
4 over a panel of 53 overexpressed receptors, including 5-HT subtypes, but does bind to human dopamine D
4 and sigma-1 (σ
1) receptors and mouse 5-HT
3 receptors (K
is = 2.3, 3.7, and 3.8 μM, respectively). It induces contractions in guinea pig colon with an EC
50 value of 33 nM, an effect that is blocked by the 5-HT
4 antagonist GR113808 but not the 5-HT
2A and 5-HT
3 antagonists ketanserin and granisetron , respectively. It also facilitates non-cholinergic contractions induced by electrical stimulation. In fasted dogs, oral administration of prucalopride increases colonic motility by inhibiting distal colon contractions (ED
50 = 0.04 mg/kg), an effect that is blocked by pretreatment with the 5-HT
4 antagonist GR125487. Prucalopride (5-10 mg/kg, s.c.) increases acetylcholine and histamine levels in the rat prefrontal cortex by 2.4-fold and 3-fold, respectively, and increases the power of hippocampal theta oscillations. Formulations containing prucalopride have been used in the treatment of chronic idiopathic constipation.
Biochem/physiol Actions
In healthy male individuals, prucalopride decreases the display of esophageal acid and promotes gastric emptying. It is effective, safe and shows good tolerance for the treatment of men with chronic constipation.
酵素阻害剤
This novel enterokinetic drug (FW = 367.87 g/mol; CAS 179474-81-8), also known by the tradename Resolor? and its systematic name, 4-amino-5- chloro-N-[1-(3-methoxypropyl)piperidin-4-yl]-2,3-dihydro-1-benzofuran-7- carboxamide, is a selective, high affinity serotonin 5-HT4 receptor agonist with that stimulates colonic mass movements, which provide the main propulsive force for defecation. It exhibits high affinity to both 5-HT4 receptor isoforms, with respective pKi values of 8.60 and 8.10 for the human 5-HT4A and 5-HT4B receptors. Based on 50 other binding assays,tonly the human D4 receptor (pKi = 5.63), the mouse 5-HT3 receptor (pKi = 5.41) and the human s1 (pKi = 5.43) shown measurable affinity, resulting in >290x selectivity for 5-HT4 receptors. Prucalopride also differs from other 5-HT4 agonists, such as tegaserod and cisapride, that interact with other receptors (5-HT1B/D and cardiac human ether-a-go-go K+ or hERG channel, respectively).
プルカロプリド 上流と下流の製品情報
原材料
準備製品