The characteristics and research progress of inverse agonists / 西安交通大学学报(医学版)

ABSTRACT

Inverse agonist is a new type of drug acting on receptors.Its research has experienced several stages, including discovery of ethylβ-carboline 3-carboxylate,activity study,proposal of the concept,two-state model,and constitutive activity theory in succession.Most G protein-coupled receptors possess constitutive activity,i.e.a proportion of receptors are in active state and can produce effects without any agonist.Inverse agonist has an affinity to receptors,but no intrinsic activity,so it cannot activate receptors.However,it can antagonize the constitutive activity of receptors,and produce an opposite effect on the corresponding agonist.Both agonist and inverse agonist can produce their effect alone with different mechanisms.Agonist activates its receptors,but inverse agonist antagonizes them.Both inverse agonist and antagonist can antagonize receptors.However,inverse agonist and antagonist antagonize the constitutive activity of receptor and the agonist’s effects,respectively.Inverse agonists can be used to treat diseases with enhanced constitutive activity,up-regulate and sensitize receptors with constitutive activity.Moreover,endogenous inverse agonists can maintain a specific physiological function.The study on inverse agonist has a theoretical significance in perfecting receptor theory as well as a clinical value in diagnosis and treatment of diseases with enhanced constitutive activity.