Title:Biased Agonism as an Emerging Strategy in the Search for Better Opioid Analgesics
Volume: 27
Issue: 9
Author(s): Justyna Piekielna-Ciesielska, Karol Wtorek and Anna Janecka*
Affiliation:
- Department of Biomolecular Chemistry, Medical University, Mazowiecka 6/8, 92-215 Lodz,Poland
Keywords:
Opioid receptors, opioid peptides, antinociceptive activity, biased agonism, bias factor, morphine.
Abstract: Morphine and related drugs that act through activating opioid receptors are the most effective
analgesics for the relief of severe pain. They have been used for decades, despite the range of unwanted
side effects that they produce, as no alternative has been found so far. The major goal of opioid
research is to understand the mechanism of action of opioid receptor agonists and to improve the
therapeutic utility of opioid drugs. In the search for safer and more potent analgesics, analogs with
mixed opioid receptor profile gained a lot of interest. However, recently the concept of biased agonism,
that highlights the fact that some ligands are able to differentially activate receptor downstream pathways,
became a new approach in the design of novel drug candidates for clinical application. In this
review, we summarize current knowledge on the development of opioid ligands of peptide and nonpeptide
structure, showing how much opioid pharmacology evolved in recent years.
