Manabe Noriaki, Rao Archana S, Wong Banny S, Camilleri Michael
Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Charlton 8-110, 200 First Street SW, Rochester, MN 55905, USA.
Curr Gastroenterol Rep. 2010 Oct;12(5):408-16. doi: 10.1007/s11894-010-0124-1.
New therapies are being developed for irritable bowel syndrome (IBS). These advances are based on understanding pathophysiology or the development of medications with greater selectivity in classes of agents with known efficacy. Prucalopride, the newest European Medicines Agency-approved 5-hydroxytryptamine receptor 4 (5-HT(4)) agonist, is effective in the treatment of chronic constipation with improved cardiovascular safety relative to older 5-HT(4) drugs; similarly, ramosetron, the 5-hydroxytryptamine receptor 3 (5-HT(3)) antagonist, appears efficacious in diarrhea-predominant IBS. Secretagogues with different mechanisms of action target apical domains in enterocytes that are involved in chloride secretion, such as chloride channels, the cystic fibrosis transmembrane regulator, and guanylate cyclase C. As a class, such secretagogues have high efficacy and safety for constipation. With more data obtained from phase 2 and 3 trials, we expect other classes of medications, including bile acid modulators, anti-inflammatory agents, visceral analgesics, and newer centrally acting agents to be efficacious and enter the armamentarium for the treatment of IBS in the future.
针对肠易激综合征(IBS)的新疗法正在研发中。这些进展基于对病理生理学的理解,或是在已知疗效的药物类别中开发出具有更高选择性的药物。普芦卡必利是欧洲药品管理局最新批准的5-羟色胺受体4(5-HT(4))激动剂,相对于 older 5-HT(4) 药物,它在治疗慢性便秘方面有效,且心血管安全性有所改善;同样,5-羟色胺受体3(5-HT(3))拮抗剂雷莫司琼在以腹泻为主的IBS中似乎有效。具有不同作用机制的促分泌剂靶向肠细胞中参与氯离子分泌的顶端结构域,如氯离子通道、囊性纤维化跨膜调节因子和鸟苷酸环化酶C。作为一类药物,此类促分泌剂对便秘具有高效性和安全性。随着从2期和3期试验中获得更多数据,我们预计其他类别的药物,包括胆汁酸调节剂、抗炎药、内脏镇痛药和更新的中枢作用药物,在未来将有效并进入治疗IBS的药物库。