Bias Factor and Therapeutic Window Correlate to Predict Safer Opioid Analgesics.
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ABSTRACT:
SUBMITTER: Schmid CL
PROVIDER: S-EPMC5731250 | biostudies-literature | 2017 Nov
REPOSITORIES: biostudies-literature
Publications
Bias Factor and Therapeutic Window Correlate to Predict Safer Opioid Analgesics.
Schmid Cullen L CL Kennedy Nicole M NM Ross Nicolette C NC Lovell Kimberly M KM Yue Zhizhou Z Morgenweck Jenny J Cameron Michael D MD Bannister Thomas D TD Bohn Laura M LM
Cell 20171101 5
Biased agonism has been proposed as a means to separate desirable and adverse drug responses downstream of G protein-coupled receptor (GPCR) targets. Herein, we describe structural features of a series of mu-opioid-receptor (MOR)-selective agonists that preferentially activate receptors to couple to G proteins or to recruit βarrestin proteins. By comparing relative bias for MOR-mediated signaling in each pathway, we demonstrate a strong correlation between the respiratory suppression/antinocicep ...[more]
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