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Biased agonism: the quest for the analgesic holy grail
M Alexander Stanczyk1, Ram Kandasamy1
1Department of Pharmacology and Edward F. Domino Research Center, University of Michigan Medical School, Ann Arbor, MI, USA.
Abstract:
Opioids alleviate pain, but adverse effects severely limit their usefulness. To solve this problem, biased ligands favoring 1 signaling pathway downstream of the μ-opioid receptor over another are being developed. In the target article, the authors synthesize compounds that preferentially activate G-protein or β-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.
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