Editorial: finding the ideal prokinetic for gastroparesis—we are not there yet

This article is linked to Kuo et al and Camilleri & papers. To view these articles, visit https://doi.org/10.1111/apt.16451 https://doi.org/10.1111/apt.16475 There an urgent need for safe effective pharmacotherapy in gastroparesis, a debilitating condition estimated affect 13.8 per 100 000 persons the United Kingdom.1 Adults with gastroparesis are recognised suffer from repeated hospitalisation, physical psychological disability, unemployment increased mortality.1, 2 Dietary modification recommended as initial management but its efficacy appears modest clinical practice.3 As delayed gastric emptying, together typical symptoms (nausea, vomiting, early satiety, postprandial fullness and/or epigastric pain), prerequisites diagnosis of drugs prokinetic effect mainstay pharmacotherapy.4 Prokinetic studied fall into one following classes: dopamine-2 antagonists, 5-HT3 5-HT4 agonists, motilin receptor agonists ghrelin agonists.4 antagonists such ondansetron granisetron, commonly used chemotherapy-induced emesis, have shown symptom improvement there lack controlled studies. 5HT4 cisapride tegaserod, although effective, been withdrawn licensed use due well-documented cardiac toxicity.5 Among class macrolide antibiotics erythromycin azithromycin clearly acute exacerbations long-term risks antibiotic resistance or tachyphylaxis led limited use.6 Relamorelin, agonist, has recently improving compared placebo,7 concerns about systemic effects on obesity worsening diabetes.8 date, metoclopramide domperidone appear most robust gastroparesis,9 first-line guidelines.3 However, both safety regarding extrapyramidal side (metoclopramide) arrhythmias (domperidone), their not advised. Hence, development similar prokinetics without would be welcome. report results pilot, multi-centre, phase 2a study trazpiroben, dopamine-2/3 antagonist among 51 (66.7% diabetic) adult patients gastroparesis.10 The was divided two parts: randomised trial three different doses drug placebo, followed by open-label comparison metoclopramide. Over short duration 9 days, investigators confirmed target (by serum prolactin levels), reported best pharmacology 25 mg dose, demonstrated no significant all doses. At end change emptying time, nor scores between trazpiroben placebo patients, patients. subjects assigned were observed greater mean volume nutrient test drink (88.5 ml vs 26.3 ml, P = 0.019). data current small sample this new promising, remains uncertain. Nevertheless, we look forward larger sized longer treatment at least 8 weeks. In meantime, search ideal continues. Declaration personal interests: None.