New developments in the treatment of gastroparesis and functional dyspepsia

•Pathophysiological research continues to focus on the role of disordered motility and visceral hypersensitivity in the pathogensis of gastroduodenal symptoms.•The role of (low grade) inflammatory changes in the mucosa and in the neuromuscular layers needs to be unraveled.•Novel prokinetics such as relamorelin, velusetrag and prucalopride are being evaluated for treatment of symptoms in FD and gastroparesis.•Restoring gastric accommodation is an emerging treatment target in FD, based on studies with acotiamide and buspirone.•A more restricted therapeutic application for specific neuromodulators in these conditions is being identified.•Early reports suggest benefit from per-endoscopic pyloric myotomy in gastroparesis, but this needs confirmation in controlled trials. Functional dyspepsia (FD) and gastroparesis are frequent causes of upper gastrointestinal symptoms such as postprandial fullness, early satiation, epigastric pain or burning, upper abdominal bloating, bothersome belching, nausea and vomiting. The underlying pathophysiological mechanisms are heterogeneous and involved mechanisms such as abnormal gastric motility (accommodation, emptying), visceral hypersensitivity, low grade mucosal inflammation and cellular changes in enteric nerves, muscle or interstitial cells of Cajal. Patient-reported outcomes for evaluating treatment efficacy in these conditions were recently developed and validated. Prokinetic agents, which enhance gastric motility, are used for treating both gastroparesis and FD. In FD, besides acid suppressive therapy and Helicobacter pylori eradication, neuromodulators and drugs that enhance gastric accommodation can be applied. In gastroparesis, anti-emetics may also provide symptom relief. Novel approaches under evaluation in these conditions are the fundus relaxing agents acotiamide and buspirone and the antidepressant mirtazapine in FD. For gastroparesis, recently studied agents include the prokinetic ghrelin agonist relamorelin, the prokinetic serotonergic agents velusetrag and prucalopride, the anti-emetic aprepitant and per-endoscopic pyloric myotomy procedures.