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Opioid receptors (ORs) represent one of the most significant groups of G-protein coupled receptor (GPCR) drug targets and also act as prototypical models for GPCR function. In a constant effort to develop drugs with less side effects, and tools to explore the ORs nature and function, various (poly)pharmacological ligand design approaches have been performed. That is, besides classical ligands, a great number of bivalent ligands (i. e. aiming on two distinct OR subtypes), univalent heteromer-selective ligands and bitopic and allosteric ligands have been synthesized for the ORs. The scope of our review is to present the most important of the aforementioned ligands, highlight their properties and exhibit the current state-of-the-art pallet of promising drug candidates or useful molecular tools for the ORs. © 2022 Wiley-VCH GmbH.


Antonios Drakopoulos, Dimitrios Moianos, Georgia-Myrto Prifti, Grigoris Zoidis, Michael Decker. Opioid Ligands Addressing Unconventional Binding Sites and More Than One Opioid Receptor Subtype. ChemMedChem. 2022 Jul 19;17(14):e202200169

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PMID: 35560796

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