Reduce efficacy, reduce side effects

Abstract

Nociception The μ-opioid receptor is an important target for pain management, but serious side effects limit the use of drugs that target this G protein–coupled receptor, which signals through both G proteins and β-arrestins. G protein–biased agonists have been developed to promote pain relief without causing β-arrestin–associated side effects. Gillis et al. noted that the observed reductions in side effects of some G protein–biased agonists of the μ-opioid receptor could be explained by their low intrinsic efficacy rather than by their signaling bias per se. Sci. Signal. 13 , eaaz3140 (2020 ).