Fig. 1.

The simple two-state model for receptor activation and the components of the total stimulus for an orthosteric agonist. a, the equilibrium of an orthosteric ligand (D) with a receptor having active (R*) and inactive states (R) is shown. K_b and K_a denote the affinity constants of D for the active and inactive states, respectively. The equilibrium constant for the relative amounts of active and inactive states in the absence of D is denoted by K_c. b, The relative amounts of receptor occupancy (DR* + DR), the stimulus (DR*), the constitutive stimulus (R*), and the total stimulus (DR* + R*) are shown as a function of the agonist concentration. The fraction of the orthosteric ligand-receptor complex in the active and inactive states is denoted by intrinsic efficacy (ε) and intrinsic inactivity (ε_i), and the fraction of the free receptor in the active and inactive states is denoted by the intrinsic efficacy of the system (ε_sys) and the intrinsic inactivity of the system (ε_i-sys), respectively.