Biased ligands at opioid receptors: Current status and future directions
- 6 April 2021
- journal article
- review article
- Published by American Association for the Advancement of Science (AAAS) in Science Signaling
- Vol. 14 (677)
- https://doi.org/10.1126/scisignal.aav0320
Abstract
The opioid crisis represents a major worldwide public health crisis that has accelerated the search for safer and more effective opioids. Over the past few years, the identification of biased opioid ligands capable of eliciting selective functional responses has provided an alternative avenue to develop novel therapeutics without the side effects of current opioid medications. However, whether biased agonism or other pharmacological properties, such as partial agonism (or low efficacy), account for the therapeutic benefits remains questionable. Here, we provide a summary of the current status of biased opioid ligands that target the μ- and κ-opioid receptors and highlight advances in preclinical and clinical trials of some of these ligands. We also discuss an example of structure-based biased ligand discovery at the μ-opioid receptor, an approach that could revolutionize drug discovery at opioid and other receptors. Last, we briefly discuss caveats and future directions for this important area of research.Keywords
Funding Information
- National Institutes of Health (RO1MH61887)
- National Institutes of Health (U19MH82441)
- European Molecular Biology Organization
- Council of Scientific and Industrial Research (14/EMR-II)
- Science and Engineering Research Board (SB/SO/BB-121/2013)
- Science and Engineering Research Board (EMR/2017/003804)
- DBT India Alliance (IA/I/14/1/501285)
- DBT India Alliance (IA/S/20/1/504916)
- National Institute of Development Administration (PO1 DA035764)
- Department of Biotechnology, Government of West Bengal (BT/08/IYBA/2014-3)
- Department of Biotechnology, Government of West Bengal (DBT BT/PR29041/BRB/10/1697/2018)
- Department of Science and Technology, Republic of the Philippines (DST/SJF/LSA-03/2017-18)
- Alzheimer Nadační Fond (DA035764)
- Engineering Research Board (EMR/2017/003804)
- DBT India Alliance (IA/I/14/1/501285)
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