The two-state model of receptor activation

Trends Pharmacol Sci. 1995 Mar;16(3):89-97. doi: 10.1016/s0165-6147(00)88989-0.


Over the past few years, the concept that the activation of G protein-coupled receptors and transmitter-gated ion channels depends on a conformational change has received increasingly widespread acceptance. As a result, these two structurally distinct families of receptors can now be considered to obey a similar two-state mechanism. However, traditional receptor theory has largely overlooked this concept. In this article, Paul Leff explains and illustrates the predictions of the two-state model of receptor activation and discusses its impact on the analysis and interpretation of agonist-receptor interactions.

MeSH terms

  • Binding, Competitive
  • Drug Design
  • GTP-Binding Proteins / metabolism*
  • Ion Channels / metabolism*
  • Ion Channels / physiology
  • Ligands
  • Models, Chemical
  • Receptors, Cell Surface / agonists
  • Receptors, Cell Surface / metabolism*


  • Ion Channels
  • Ligands
  • Receptors, Cell Surface
  • GTP-Binding Proteins