BioAcyl Corp
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Burford, N. T., Traynor, J. R., & Alt, A. (2015). Positive allosteric modulators of the μ-opioid receptor: A novel approach for future pain medications. British Journal of Pharmacology, 172(2), 277–286. Added by: Dr. Enrique Feoli (29/11/2023, 20:26) Last edited by: Dr. Enrique Feoli (29/11/2023, 20:29) |
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| Resource type: Journal Article DOI: https://doi.org/10.1111/bph.12599 BibTeX citation key: Burford2015 View all bibliographic details  |
Categories: BioAcyl Corp Subcategories: Positive allosteric modulators Creators: Alt, Burford, Traynor Collection: British Journal of Pharmacology |
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| Abstract |
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Morphine and other agonists of the μ-opioid receptor are used clinically for acute and chronic pain relief and are considered to be the gold standard for pain medication. However, these opioids also have significant side effects, which are also mediated via activation of the μ-opioid receptor. Since the latter half of the twentieth century, researchers have sought to tease apart the mechanisms underlying analgesia, tolerance and dependence, with the hope of designing drugs with fewer side effects. These efforts have revolved around the design of orthosteric agonists with differing pharmacokinetic properties and/or selectivity profiles for the different opioid receptor types. Recently, μ-opioid receptor-positive allosteric modulators (μ-PAMs) were identified, which bind to a (allosteric) site on the μ-opioid receptor separate from the orthosteric site that binds an endogenous agonist. These allosteric modulators have little or no detectable functional activity when bound to the receptor in the absence of orthosteric agonist, but can potentiate the activity of bound orthosteric agonist, seen as an increase in apparent potency and/or efficacy of the orthosteric agonist. In this review, we describe the potential advantages that a μ-PAM approach might bring to the design of novel therapeutics for pain that may lack the side effects currently associated with opioid therapy. Linked Articles This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2
Modes of allosteric modulation. Allosteric ligands (B) bind to a topographically distinct site on the receptor compared with the orthosteric agonist (A), and can modulate orthosteric agonist binding affinity (α), orthosteric agonist efficacy (β), and may have intrinsic agonist activity (τB). Cartoon is a modified figure from Conn et al., 2009a. Added by: Dr. Enrique Feoli Last edited by: Dr. Enrique Feoli |
