Guanylate cyclase C‐mediated antinociceptive effects of linaclotide in rodent models of visceral pain

@article{Eutamene2010GuanylateCC,
  title={Guanylate cyclase C‐mediated antinociceptive effects of linaclotide in rodent models of visceral pain},
  author={Helene Eutamene and Sylvie Bradesi and Muriel Larauche and V. Theodorou and Catherine Beaufrand and Gordon Ohning and Jean Fioramonti and M Cohen and Alexander P. Bryant and Caroline B. Kurtz and Mark G. Currie and Emeran A. Mayer and Lionel Bu{\'e}no},
  journal={Neurogastroenterology \& Motility},
  year={2010},
  volume={22}
}
Background  Linaclotide is a novel, orally administered investigational drug currently in clinical development for the treatment of constipation‐predominant irritable bowel syndrome (IBS‐C) and chronic idiopathic constipation. Visceral hyperalgesia is a major pathophysiological mechanism in IBS‐C. Therefore, we investigated the anti‐nociceptive properties of linaclotide in rodent models of inflammatory and non‐inflammatory visceral pain and determined whether these pharmacological effects are… 
Linaclotide – a secretagogue and antihyperalgesic agent – what next?
  • A. Bharucha, D. R. Linden
  • Medicine
    Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
  • 2010
TLDR
The data suggest that GC‐C receptors exert other, as yet poorly understood, effects on gastrointestinal sensitivity in conditions associated with inflammation and/or stress‐induced increased intestinal permeability, however, the data need to be confirmed in humans and in long‐term animal models.
Clinical evidence for the role of linaclotide for the treatment of irritable bowel syndrome
TLDR
Linaclotide is an exciting new drug arriving timely to assist clinicians in the management of IBS-C, a benign yet common, and extremely inconvenient symptomatic condition that currently poses a significant therapeutic challenge.
Linaclotide, a synthetic guanylate cyclase C agonist, for the treatment of functional gastrointestinal disorders associated with constipation
TLDR
Linaclotide is a novel drug, with a unique mechanism of action, low bioavailability and local action in the intestinal epithelial cells, currently being developed for patients with CC and IBS-C.
Emerging receptor target in the pharmacotherapy of irritable bowel syndrome with constipation
TLDR
The evidence base supporting the role of guanylate cyclase C (GC-C) activation in the modulation of gastrointestinal transit and, in particular, in visceral hypersensitivity is described.
Linaclotide inhibits colonic and urinary bladder hypersensitivity in adult female rats following unpredictable neonatal stress
TLDR
The hypothesis that linaclotide will reverse colon and bladder hyperalgesia in a female‐specific rodent model of adverse early life experience is tested.
Anti-nociceptive effect of Faecalibacterium prausnitzii in non-inflammatory IBS-like models
TLDR
F. prausnitzii exhibits anti-nociceptive properties, indicating its potential to treat abdominal pain in IBS patients and significantly decreased colonic hypersensitivity induced by either NMS in mice or partial restraint stress in rats.
Peripheral Guanylate Cyclase‐C modulation of corticolimbic activation and corticotropin‐releasing factor signaling in a rat model of stress‐induced colonic hypersensitivity
TLDR
The hypothesis that GC‐C agonism reverses stress‐induced colonic hypersensitivity via inhibition of nociceptive afferent signaling resulting in normalization of stress‐altered corticotropin‐releasing factor (CRF) expression in brain regions involved in pain perception and modulation is tested.
Linaclotide: A new drug for the treatment of chronic constipation and irritable bowel syndrome with constipation
TLDR
Linaclotide showed a favourable safety profile, and the main treatment-emerging adverse event was diarrhea, leading to discontinuation rates of up to 5%, which is an important addition to the therapeutic possibilities for treating IBS-C and CC.
Linaclotide Attenuates Visceral Organ Crosstalk: Role of Guanylate Cyclase-C Activation in Reversing Bladder-Colon Cross-Sensitization
TLDR
The hypothesis that linaclotide, a guanylate cyclase-C (GC-C) agonist approved for the treatment of IBS with constipation (IBS-C), may represent a novel therapeutic for BPS acting through a mechanism involving an inhibition of visceral organ cross-sensitization is tested.
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