[2] Functional selectivity, or biased signaling, is most extensively characterized at G protein coupled receptors (GPCRs).
For example, pre-clinical studies with G protein biased agonists at the μ-opioid receptor show equivalent efficacy for treating pain with reduced risk for addictive potential and respiratory depression.
[1][6] Studies within the chemokine receptor system also suggest that GPCR biased agonism is physiologically relevant.
For instance, a ligand can not easily be classified as an agonist or antagonist, because it can be a little of both, depending on its preferred signal transduction pathways.
(Conversely, LSD, unlike serotonin, has negligible affinity for the 5-HT2C-VGV isoform, is unable to promote calcium release, and is, thus, functionally selective at 5-HT2C.
[12] However, recent reports highlight that, rather than functional selectivity or 'G protein bias', this agonist has low intrinsic efficacy.