title: Novel approaches to the pharmacological blockade of gastric acid secretion.
abstract: Research into new methods of controlling acid secretion is driven by existing medical needs in gastro-oesophageal reflux disease treatment. Histamine receptor subtype 3 agonists offer one approach for acid inhibition but no agent is yet undergoing clinical testing. Other, as yet unrealized strategies include preventing the fusion of the tubulovesicular elements that contain H+/K+-ATPase with the parietal cell membrane, or blocking channels that recycle K+ in the parietal cell. Of more promise are gastrin (cholecystokinin) receptor antagonists and potassium-competitive acid blockers; examples of both are in clinical development. It is probable that gastrin receptor antagonists would be used adjunctively with proton pump inhibitors, possibly for meal-induced reflux. The potassium-competitive acid blockers have attributes that may facilitate use as monotherapy for the treatment of gastro-oesophageal reflux disease. The early promise of gastrin receptor antagonists and potassium-competitive acid blockers remains to be defined in large-scale trials.
authors.affiliation: Department of Biosciences, University of Hertfordshire, Hatfield, Hertfordshire AL10 9AB, UK. m.e.parsons@herts.ac.uk
authors.forename: Michael E
authors.initials: ME
authors.lastname: Parsons
authors.forename: David J
authors.initials: DJ
authors.lastname: Keeling
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000378:metabolism; D005765:Gastrointestinal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism; D017442:Histamine Agonists / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D054328:Proton Pump Inhibitors; D017494:Proton Pumps / Q000378:metabolism; D043887:Receptor, Cholecystokinin B / Q000037:antagonists & inhibitors / Q000378:metabolism; D018100:Receptors, Histamine H3 / Q000187:drug effects / Q000378:metabolism
chemical_list: D005765:Gastrointestinal Agents; D017442:Histamine Agonists; D026902:Potassium Channel Blockers; D054328:Proton Pump Inhibitors; D017494:Proton Pumps; D043887:Receptor, Cholecystokinin B; D018100:Receptors, Histamine H3; D017506:H(+)-K(+)-Exchanging ATPase