Ligand bias refers to the ability of a drug at a receptor to activate selectively particular cell signalling pathways over others, in a way that cannot be explained by traditional models of receptor theory. For a physiologically and therapeutically important GPCR (G-protein-coupled receptor) such as the MOPr (μ-opioid receptor), the role of ligand bias is currently being explored, not only in order to understand the molecular function of this receptor, but also with a view to developing better analgesic drugs with fewer adverse effects. In this short review, the ways to detect and quantify agonist bias at MOPr are discussed, along with the possible significance of MOPr ligand bias in the therapeutic use of opioid drugs. An important conclusion of this work is that attempts to define ligand bias at any GPCR on the basis of the visual inspection of concentration–response curves or comparison of maximum response (Emax) values can be misleading. Instead, reliable estimations of relative agonist efficacy are needed to calculate bias effectively.

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