Motilin, ghrelin and related neuropeptides as targets for the treatment of GI diseases

Motilin and ghrelin are released from the upper gut during fasting, to stimulate gastric motility. Additional actions of ghrelin (e.g. changes in appetite, nausea or endocrine functions) improve the possibility of using ghrelin receptor agonists to treat complex disorders such as functional dyspepsia. However, changes in endocrine functions increase the risk of unacceptable side effects. By comparison, the more restricted prokinetic activity of motilin limits the therapeutic possibilities but improves the risk:benefit ratio. Compounds targeting both receptors are in development. Recently, additional peptides have been identified from preproghrelin (obestatin) and prepromotilin. These exert biological activity but their pathophysiological significance is unknown.