Drugs under development for the treatment of functional dyspepsia and related disorders

ABSTRACT

Introduction: 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.Areas covered: This review summarizes recent and ongoing drug development for FD as identifiedExpert opinion: 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.

KEYWORDS:

• Functional dyspepsia
• postprandial distress syndrome
• epigastric pain syndrome
• proton pump inhibitors
• prokinetics
• histamine receptor blockers
• neuromodulators
• potassium-competitive acid blockers
• herbal medicines

Article highlights

• Functional dyspepsia (FD) is one of the most common gastrointestinal disorders, but there are few therapies of established efficacy

• Stronger acid suppressive therapy with potassium-competitive acid blockers have a potential to provide better symptom control through stronger acid suppression

• New prokinetics potentially applicable to FD include dopamine-2 receptor antagonists and 5-HT4 agonists

• Fundic relaxant agents are a new therapeutic approach, including acotiamide and azapirones

• Centrally but also peripherally acting neuromodulators can provide benefit by acting on visceral hypersensitivity

• Low-grade duodenal inflammation may be a novel target for therapy, using histamine or leukotriene receptor antagonists, acid suppressive agents and perhaps pro- and antibiotics

• New validated patient reported outcome questionnaires for FD studies are becoming available

This box summarizes the key points contained in the article.

Declaration of interest

J Tack has given Scientific advice to AlfaWassermann, Allergan, Christian Hansen, Danone, Grünenthal, Ironwood, Janssen, Kiowa Kirin, Menarini, Mylan, Neutec, Novartis, Noventure, Nutricia, Shionogi, Shire, Takeda, Theravance, Tramedico, Truvion, Tsumura, Zealand and Zeria pharmaceuticals and has served on the Speaker bureau for Abbott, Allergan, AstraZeneca, Janssen, Kyowa Kirin, Menarini, Mylan, Novartis, Shire, Takeda, Truvion and Zeria. T Vanuytsel has given scientific advice to Dr. Falk, Shire, Takeda, Therachon, Tramedico, and Zealand and has served on the speaker bureau for Abbott, Kyowa Kirin, Menarini, Truvion and Will Pharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded