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Brierley SM, Grundy L, Castro J, et al. Guanylate cyclase-C agonists as peripherally acting treatments of chronic visceral pain. Trends Pharmacol Sci. 2021;doi: 10.1016/j.tips.2021.11.002.
Brierley, S. M., Grundy, L., Castro, J., Harrington, A. M., Hannig, G., & Camilleri, M. (2021). Guanylate cyclase-C agonists as peripherally acting treatments of chronic visceral pain. Trends in pharmacological sciences, . https://doi.org/10.1016/j.tips.2021.11.002
Brierley, Stuart M, et al. "Guanylate cyclase-C agonists as peripherally acting treatments of chronic visceral pain." Trends in pharmacological sciences vol. (2021). doi: https://doi.org/10.1016/j.tips.2021.11.002
Brierley SM, Grundy L, Castro J, Harrington AM, Hannig G, Camilleri M. Guanylate cyclase-C agonists as peripherally acting treatments of chronic visceral pain. Trends Pharmacol Sci. 2021 Dec 02; doi: 10.1016/j.tips.2021.11.002. Epub 2021 Dec 02. PMID: 34865885.
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Trends Pharmacol Sci. 2021 Dec 02; doi: 10.1016/j.tips.2021.11.002. Epub 2021 Dec 02.

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

Trends in pharmacological sciences

Stuart M Brierley, Luke Grundy, Joel Castro, Andrea M Harrington, Gerhard Hannig, Michael Camilleri

Affiliations

  1. Visceral Pain Research Group, College of Medicine and Public Health, Flinders Health and Medical Research Institute (FHMRI), Flinders University, Bedford Park, South Australia 5042, Australia; Hopwood Centre for Neurobiology, Lifelong Health Theme, South Australian Health and Medical Research Institute (SAHMRI), North Terrace, Adelaide, South Australia 5000, Australia; Discipline of Medicine, University of Adelaide, North Terrace, Adelaide, South Australia 5000, Australia. Electronic address: [email protected].
  2. Visceral Pain Research Group, College of Medicine and Public Health, Flinders Health and Medical Research Institute (FHMRI), Flinders University, Bedford Park, South Australia 5042, Australia; Hopwood Centre for Neurobiology, Lifelong Health Theme, South Australian Health and Medical Research Institute (SAHMRI), North Terrace, Adelaide, South Australia 5000, Australia.
  3. Ironwood Pharmaceuticals, Boston, MA, USA.
  4. Clinical Enteric Neuroscience Translational and Epidemiologic Research Program, Mayo Clinic, Rochester, MN, USA.

PMID: 34865885 DOI: 10.1016/j.tips.2021.11.002

Abstract

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.

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Keywords: afferents; cross-organ sensitization; cyclic guanosine monophosphate; irritable bowel syndrome; linaclotide; pain

Conflict of interest statement

Declaration of interests G.H. was an employee of Ironwood Pharmaceuticals and owns stock/stock options in Ironwood Pharmaceuticals. S.M.B. received grant support from Ironwood Pharmaceuticals to condu

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