Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
, 15 (3), 598-611

Inverse, Protean, and Ligand-Selective Agonism: Matters of Receptor Conformation

Affiliations
Review

Inverse, Protean, and Ligand-Selective Agonism: Matters of Receptor Conformation

T Kenakin. FASEB J.

Abstract

Concepts regarding the mechanisms by which drugs activate receptors to produce physiological response have progressed beyond considering the receptor as a simple on-off switch. Current evidence suggests that the idea that agonists produce only varying degrees of receptor activation is obsolete and must be reconciled with data to show that agonist efficacy has texture as well as magnitude. Thus, agonists can block system constitutive response (inverse agonists), behave as positive and inverse agonists on the same receptor (protean agonists), and differ in the stimulus pattern they produce in physiological systems (ligand-selective agonists). The molecular mechanism for this seemingly diverse array of activities is the same, namely, the selective microaffinity of ligands for different conformational states of the receptor. This paper reviews evidence for the existence of the various types of agonism and the potential therapeutic utility of different agonist types.-Kenakin, T. Inverse, protean, and ligand-selective agonism: matters of receptor conformation.

Similar articles

See all similar articles

Cited by 92 articles

See all "Cited by" articles

LinkOut - more resources

Feedback