Early investigational therapeutics for gastrointestinal motility disorders: from animal studies to Phase II trials

Abstract

Introduction: The most common gastrointestinal disorders that include evidence of dysmotility include: gastroparesis, the lower functional gastrointestinal disorders associated with altered bowel function (such as chronic [functional] diarrhea, chronic idiopathic constipation) and opioid-induced constipation. These conditions, which are grouped as gastrointestinal motility and functional disorders, are characterized by abnormal motor, sensory or secretory functions that alter bowel function and result in a significant disease burden, since currently available treatments do not completely alleviate symptoms. New drugs are being developed for these disorders, targeting mechanisms involved in the pathophysiology of these diseases, specifically, motor function, intestinal secretion and bile acid modulation.

Areas covered: The article provides a brief overview of motility disorders and the drugs approved and currently available for these indications. It also provides an evaluation of the efficacy, safety and possible mechanisms of the drugs currently under investigation for the treatment of gastroparesis, chronic diarrhea, chronic idiopathic constipation and opioid-induced constipation, based on animal to Phase II studies. Medications with complete Phase III trials are excluded from this discussion.

Expert opinion: Treatment of gastrointestinal motility disorders requires the understanding of the pathophysiological mechanisms, biomarkers to identify subgroups of these disorders and robust pharmacological studies from animal to Phase II studies. These are prerequisites for the development of efficacious medications and individualizing therapy in order to enhance the treatment of these patients.

Keywords: acetylcholine; agonist; antagonist; bile acids; ghrelin; motilin; opioids; pharmacology; receptor; serotonin.