Serotonin receptor modulators in the treatment of irritable bowel syndrome.
Serotonin receptor modulators in the treatment of irritable bowel syndrome.
复制标题
DOI：
10.2147/tcrm.s140
复制
发表时间：
2008-02
影响因子：
2.8
通讯作者：
Lackner JM
中科院分区：
文献类型：
--
作者：
Fayyaz M;Lackner JM
本文的目的是审查的病理生理和临床作用的5-羟色胺受体调节剂用于治疗肠易激综合征。5-羟色胺是一种重要的单胺类神经递质，在蠕动反射和分泌反射的启动以及内脏感觉的调节中起关键作用。几种5-羟色胺受体亚型已被鉴定，其中5 HT 3、5 HT 4和5 HT 1b对GI功能最重要。5 HT 4激动剂（例如，替加色罗）可增强由5 HT 1受体刺激引发的糖尿病。因此，5 HT 4激动剂可用于便秘为主的IBS形式和慢性便秘。5-HT 3拮抗剂（阿洛司琼和西兰司琼）可阻止外源性传入神经元上5-HT 3受体的激活，并可减轻IBS相关的内脏痛。这些药物还可延缓小肠和结肠转运，因此可用于治疗肠易激综合征。在几项随机、安慰剂对照试验中，已证明替加色罗可缓解整体IBS症状以及腹部不适、排便次数和粪便粘稠度的个体症状。几项随机对照试验表明，阿洛司琼缓解疼痛，改善肠功能，并提供全球症状改善妇女肠易激综合征。然而，缺血性结肠炎和便秘的严重并发症一直是导致阿洛司琼自愿退出市场的主要问题，随后通过全面的风险管理计划重新上市。
The aim of this article is to review the pathophysiology and clinical role of serotonin receptor modulators used in the treatment of irritable bowel syndrome. Serotonin is an important monoamine neurotransmitter that plays a key role in the initiation of peristaltic and secretory refl exes, and in modulation of visceral sensations. Several serotonin receptor subtypes have been characterized, of which 5HT3, 5HT4, and 5HT1b are the most important for GI function. 5HT4 agonists (eg, tegaserod) potentiate peristalsis initiated by 5HT1 receptor stimulation. 5HT4 agonists are therefore useful in constipation predominant form of IBS and in chronic constipation. 5HT3 antagonists (Alosetron and Cilansetron) prevent the activation of 5HT3 receptors on extrinsic afferent neurons and can decrease the visceral pain associated with IBS. These agents also retard small intestinal and colonic transit, and are therefore useful in diarrhea-predominant IBS. Tegaserod has been demonstrated in several randomized, placebo controlled trials to relieve global IBS symptoms as well as individual symptoms of abdominal discomfort, number of bowel movements and stool consistency. Several randomized, controlled trials have shown that alosetron relieves pain, improves bowel function, and provides global symptom improvement in women with diarrhea-predominant irritable bowel syndrome. However, ischemic colitis and severe complications of constipation have been major concerns leading to voluntary withdrawal of Alosetron from the market followed by remarketing with a comprehensive risk management program.