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Therapeutic potential of allosteric modulators for the treatment of gastrointestinal motility disorders.
  • +2
  • Ayame Saito,
  • Sadia Alvi,
  • Celine Valant,
  • Simona Carbone,
  • Daniel Poole
Ayame Saito
Monash Institute of Pharmaceutical Sciences

Corresponding Author:ayame.saito1@monash.edu

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Sadia Alvi
Monash Institute of Pharmaceutical Sciences
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Celine Valant
Monash Institute of Pharmaceutical Sciences
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Simona Carbone
Monash Institute of Pharmaceutical Sciences
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Daniel Poole
Monash Institute of Pharmaceutical Sciences
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Abstract

Gastrointestinal motility is tightly regulated by the enteric nervous system (ENS). Disruption of coordinated ENS activity can result in dysmotility. Pharmacological treatment options for dysmotility include targeting of G protein-coupled receptors (GPCRs) expressed by neurons of the ENS. Current GPCR-targeting drugs for motility disorders bind to the highly conserved endogenous ligand binding site and promote indiscriminate activation or inhibition of the target receptor throughout the body. This can be associated with significant side-effect liability and a loss of physiological tone. Allosteric modulators of GPCRs bind to a distinct site from the endogenous ligand, which is typically less conserved across multiple receptor subtypes and can modulate endogenous ligand signalling. Allosteric modulation of GPCRs that are important for ENS function may provide effective relief from motility disorders while limiting side-effects. This review will focus on how allosteric modulators of GPCRs may influence gastrointestinal motility, using 5-HT, ACh, and opioid receptors as examples.
22 Sep 2022Submitted to British Journal of Pharmacology
22 Sep 2022Submission Checks Completed
22 Sep 2022Assigned to Editor
29 Sep 2022Reviewer(s) Assigned
27 Oct 2022Review(s) Completed, Editorial Evaluation Pending
28 Oct 2022Editorial Decision: Revise Minor
17 Nov 20221st Revision Received
29 Nov 2022Submission Checks Completed
29 Nov 2022Assigned to Editor
08 Dec 2022Review(s) Completed, Editorial Evaluation Pending