Saad Richard J, Chey William D
Division of Gastroenterology, Department of Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA.
Expert Opin Investig Drugs. 2008 Feb;17(2):117-30. doi: 10.1517/13543784.17.2.117.
There is tremendous activity and excitement in the arena of drug development for the treatment of the irritable bowel syndrome (IBS). Pharmacologic therapy has been largely limited to gut acting therapeutic agents including antidiarrheals, laxatives and antispasmodics that primarily target individual symptoms. Various antidepressants have gained popularity although their efficacy in clinical trials has been modest and their clinical utility is limited by untoward side effects. Serotonergic agents have demonstrated efficacy on the global symptoms of IBS; however, recent concerns about safety have severely limited their use. Recent discoveries regarding the pathophysiology of IBS have revealed numerous potential therapeutic targets. Agents under development include newer serotonergic agents and antidepressants; chloride channel, guanylate cyclase, opioid and motilin receptor ligands; various central, peripheral and autonomic neural receptor ligands; and gut immune modulators.
在肠易激综合征(IBS)治疗的药物研发领域,有大量的研究活动且令人兴奋。药物治疗在很大程度上局限于作用于肠道的治疗药物,包括主要针对个体症状的止泻药、泻药和抗痉挛药。各种抗抑郁药虽已受到欢迎,但其在临床试验中的疗效一般,且其临床应用因不良副作用而受限。5-羟色胺能药物已显示出对IBS整体症状的疗效;然而,最近对安全性的担忧严重限制了它们的使用。关于IBS病理生理学的最新发现揭示了众多潜在的治疗靶点。正在研发的药物包括新型5-羟色胺能药物和抗抑郁药;氯离子通道、鸟苷酸环化酶、阿片样物质和胃动素受体配体;各种中枢、外周和自主神经受体配体;以及肠道免疫调节剂。