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Papers of the Week

Papers: 4 Dec 2021 - 10 Dec 2021

Pharmacology/Drug Development

2021 Dec 02

Trends Pharmacol Sci

Guanylate cyclase-C agonists as peripherally acting treatments of chronic visceral pain.


Brierley SM, Grundy L, Castro J, Harrington AM, Hannig G, Camilleri M
Trends Pharmacol Sci. 2021 Dec 02.
PMID: 34865885.


Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain and altered bowel habit that affects ~11% of the global population. Over the past decade, preclinical and clinical studies have revealed a variety of novel mechanisms relating to the visceral analgesic effects of guanylate cyclase-C (GC-C) agonists. Here we discuss the mechanisms by which GC-C agonists target the GC-C/cyclic guanosine-3',5'-monophosphate (cGMP) pathway, resulting in visceral analgesia as well as clinically relevant relief of abdominal pain and other sensations in IBS patients. Due to the preponderance of evidence we focus on linaclotide, a 14-amino acid GC-C agonist with very low oral bioavailability that acts within the gut. Collectively, the weight of experimental and clinical evidence supports the concept that GC-C agonists act as peripherally acting visceral analgesics.