Biased Agonism: The Quest For The Analgesic Holy Grail

Opioids alleviate pain, but adverse effects severely limit their usefulness. To solve this problem, biased ligands favoring 1 signaling pathway downstream of them-opioid receptor over another are being developed. In the target article, the authors synthesize compounds that preferentially activate G-protein or beta-arrestin signaling. They find that increased bias towards G-protein signaling produces better antinociception with minimal side effects in mice models. G-protein-biased opioids may provide a safer treatment strategy.