Fig. 1.

Hypothesis for increased analgesia and reduced adverse events for a biased G protein μ-opioid receptor ligand. Morphine binding to the μ-opioid receptor (left) engages analgesic signaling through G protein coupling to inhibit nociception by neuronal hyperpolarization and also engages β-arrestins to the same receptor, which inhibits G protein coupling and promotes respiratory depression and constipation. TRV130 is a G protein-biased ligand that engages G protein coupling similarly to morphine, but with less β-arrestin recruitment. [Reproduced from Ref. 68.]