Recent developments in gastrointestinal prokinetic agents

Abstract

Background: Prokinetic agents are employed to reverse impaired gastrointestinal motility arising from functional disorders such as constipation-dependent irritable bowel syndrome and functional dyspepsia, as well as chronic constipation and gastro-oesophageal reflux disease. Postoperative ileus, diabetic gastroparesis and delayed gastric emptying in critically ill patients may also be treated with prokinetics. Over the last few years, some clinically effective gastro-prokinetic agents have been withdrawn or suspended from the market, which has created additional unmet medical need in this area. Objective: To assess critically the recent literature on prokinetic agents, with a primary focus on patents covering known and novel mechanisms of action, as well as updating the current status of selected compounds in clinical development as prokinetics. Methods: Patents were searched between 2005 and 2007, using a combination of Scifinder, Investigational Drugs Database and Prous databases. Results/conclusion: Prokinetic agents represent a significant unmet medical need and remain an active area of research for the pharmaceutical industry. Recent activities are divided between novel targets such as motilin receptor agonists, ghrelin receptor agonists and prosecretory agents, together with improvement of existing mechanisms of action, especially serotonin 5-HT₄ receptor agonists. A number of compounds from both categories are currently in clinical development.

Keywords::

• constipation
• delayed gastric emptying
• gastro-oesophageal reflux disease
• gastroparesis
• ghrelin receptor agonists
• guanylate cyclase-C activators
• irritable bowel syndrome
• motilin receptor agonists
• serotonin 5-HT₄ receptor agonists
• type-2 chloride channel activators