title: Investigational drug therapies for the treatment of gastroparesis.
abstract: Gastroparesis is defined by nausea, vomiting, pain, early satiety and bloating, and characterized by delayed gastric emptying without obvious structural abnormalities. Metoclopramide is widely used, increasing gastric emptying and inhibiting nausea and vomiting. Other drugs are available in certain countries and some are used 'off-label' because they increase gastric emptying or inhibit emesis. However, correlation between gastroparesis symptoms and rates of gastric emptying is poor. For anti-emetic drugs, dose-ranging and Phase III trials in gastroparesis are lacking. Areas covered: Gastric motility may still be disordered, leading to nausea, even though gastric emptying is unchanged. One hypothesis is that interstitial cells of Cajal (ICC) are damaged by diabetes leading to gastric dysrhythmia and nausea. Novel approaches to treatment of nausea also include the use of ghrelin receptor agonists, highlighting a link between appetite and nausea. Expert opinion: There is an urgent need to diversify away from historical drug targets. In particular, there is a need to control nausea by regulating ICC functions and/or by facilitating appetite via ghrelin receptor agonists. It is also important to note that different upper gastrointestinal disorders (gastroparesis, chronic unexplained nausea and vomiting, functional dyspepsia) are difficult to distinguish apart, suggesting wider therapeutic opportunity.
authors.affiliation: a Professor of Neuropharmacology , Blizard Institute and the National Centre for Bowel Research, Barts The London School of Medicine and Dentistry, Queen Mary University of London , London , UK.
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Sanger
authors.affiliation: b Vice Chair of Medicine for Innovation and Commercialization , Johns Hopkins University School of Medicine, Director, Johns Hopkins Center for Neurogastroenterology, Professor of Medicine and Neurosciences, Professor of Innovation Management, Johns Hopkins Carey School of Business , Baltimore , MD , USA.
authors.forename: Pankaj Jay
authors.initials: PJ
authors.lastname: Pasricha
mesh_terms: D000818:Animals; D015195:Drug Design; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use*; D005746:Gastric Emptying / Q000187:drug effects; D005765:Gastrointestinal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005769:Gastrointestinal Motility / Q000187:drug effects; D018589:Gastroparesis / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D056885:Interstitial Cells of Cajal / Q000473:pathology; D009325:Nausea / Q000188:drug therapy / Q000209:etiology; D014839:Vomiting / Q000188:drug therapy / Q000209:etiology
chemical_list: D015507:Drugs, Investigational; D005765:Gastrointestinal Agents
keywords: Gastric motility; gastroparesis; ghrelin; interstitial cells of Cajal; nausea