Functional selectivity

Recently, a novel theory called Functional Selectivity (also referred to in the literature as “agonist trafficking”, “biased agonism”, “differential engagement” and “protean agonism”) has been proposed to broaden conventional definitions of pharmacology. Traditional pharmacology posits that a ligand can be either classified as an agonist (full or partial), antagonist or more recently an inverse agonist (observed in systems with adequate constitutive activity) through a specific receptor subtype, and that this characteristic will be consistent with all effector systems coupled to that receptor. While this dogma has been the backbone of ligand-receptor interactions for decades now, more recent data indicates that this classic definition of ligand-protein associations does not hold true for a number of compounds. In fact, the literature suggests that a ligand may inherently produce a mix of the classic characteristics through a single receptor isoform depending on the effector pathway coupled to that receptor. It is also important to note that these observations were made in a number of different expression systems and therefore functional selectivity is not just an epiphenomenon of one particular expression system.