Novel investigational drugs for constipation-predominant irritable bowel syndrome: a review

ABSTRACT

Introduction: Constipation-predominant irritable bowel syndrome (IBS-C) is a functional gastrointestinal (GI) disorder with an unknown etiology. A number of the drugs tested for IBS-C have also been applied to chronic constipation and chronic idiopathic constipation. Unfortunately, due to severe adverse effects, many drugs envisioned for IBS-C had been withdrawn from the market. Nevertheless, a number of potential new agents for this indication are now under development.

Areas covered: The following review describes the most recently developed agents in preclinical as well as Phase 1 and Phase 2 clinical studies. Information was obtained from published literature, abstracts and the latest results found in Clinicaltrial.gov database. The authors put a special interest on glucagon-like peptide 1 analogue, bile acid modulators, serotonergic agents, guanylate cyclase C and cannabinoid antagonists.

Expert opinion: To enter the market, a newly-developed drug has to meet several criteria, such as good bioavailability or the absence of drug-related adverse events. Taking into account constipation and abdominal pain as the main symptoms in IBS-C, a novel successful drug is usually able to improve both at the same time. Four out of fifteen investigational drugs described in this paper belong to the serotonergic family and have a good prognosis to reach the market; still, more long-term clinical studies are warranted.

KEYWORDS:

• constipation-predominant irritable bowel syndrome
• GLP-1 analogue
• serotonin
• guanylate cyclase C
• bile acid transporter
• chloride channels
• cannabinoid

Financial and Competing Interests Disclosure

The authors are supported by the Medical University of Lodz [Project “UMED Grants” 63/2014-2015 to P Mosińska, 502-03/1-156-04/502-14-140 to M Salaga and #503/1-156-04/503-01 to J Fichna] and the National Science Centre [#UMO-2015/16/T/NZ7/00031 and #UMO-2013/11/N/NZ7/02354 to M Salaga, #UMO-2013/11/B/NZ7/01301 and #UMO-2014/13/B/NZ4/01179 to J Fichna]. This study is also sponsored by the Polpharma Scientific Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.