Translational Research Centre for Gastrointestinal Disorders, University of Leuven , Leuven , Belgium.
Expert Opin Investig Drugs. 2019 Oct;28(10):871-889. doi: 10.1080/13543784.2019.1673365. Epub 2019 Oct 8.
: Functional dyspepsia (FD), defined as the presence of chronic functional symptoms originating from the gastroduodenal, is one of the most common functional gastrointestinal disorders. FD is subdivided into postprandial distress syndrome (PDS), with meal-related symptoms such as postprandial fullness and early satiation, and epigastric pain syndrome (EPS), with meal-unrelated symptoms such as epigastric pain or burning. Therapeutic options for FD are very limited, probably reflecting the complex pathophysiology which comprises disorders of gastric sensorimotor function as well as low-grade duodenal inflammation.: This review summarizes recent and ongoing drug development for FD as identified: Proton pump inhibitors (PPIs) are the traditional first-line therapy while potassiumcompetitive acid blockers are being studied. Ongoing drug development focuses on gastric motility with prokinetics (dopamine-2 antagonists and 5-HT4 agonists) and fundus relaxant therapies (acotiamide, azapirones), and on sensitivity with peripherally (guanylate cyclase and cannabinoid agonists) and centrally acting neuromodulators. Drugs under development for gastroparesis may be efficacious in PDS. There are emerging data with pro-and antibiotics and with phytotherapeutic agents. Duodenal low-grade inflammation is a newly emerging target which may respond also to PPIs, histamine and leukotriene receptor blockers.
功能性消化不良(FD)是指源于胃十二指肠的慢性功能性症状,是最常见的功能性胃肠道疾病之一。FD 分为餐后不适综合征(PDS),其症状与进餐相关,如餐后饱胀和早饱;以及上腹疼痛综合征(EPS),其症状与进餐无关,如上腹疼痛或烧灼感。FD 的治疗选择非常有限,这可能反映了其复杂的病理生理学,包括胃感觉运动功能障碍以及低度十二指肠炎症。
本综述总结了最近和正在进行的 FD 药物开发,包括:质子泵抑制剂(PPIs)是传统的一线治疗药物,而钾竞争性酸阻滞剂正在研究中。正在进行的药物开发侧重于胃动力,包括促动力药(多巴胺-2 拮抗剂和 5-HT4 激动剂)和胃底松弛治疗(阿考替胺、阿扎匹隆),以及敏感性治疗,包括外周(鸟苷酸环化酶和大麻素激动剂)和中枢作用的神经调节剂。用于治疗胃轻瘫的药物可能对 PDS 有效。正在开发的用于治疗幽门螺杆菌感染和植物治疗剂的药物也有新的进展。十二指肠低度炎症是一个新出现的靶点,可能对 PPI、组胺和白三烯受体阻滞剂也有反应。