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. 2013 Jun 21;169(6):1189–1202. doi: 10.1111/bph.12231

Figure 1.

Figure 1

(A) The two-state model of agonism: four receptor species, two free (R, inactive and R*, active) and two ligand-bound (AR, inactive and AR*, active). Because of the thermodynamic cycle, there are four equilibrium constants but only three independent parameters, L, K and α. L measures the propensity of the free receptor to form active states; K, the affinity of the ligand A for the inactive receptor state; and α, the intrinsic efficacy of the ligand viewed either as the capacity to alter L in the complexed relative to the free receptors (horizontal equilibria) or the differential affinity for binding to inactive and active receptors (vertical equilibria). The functional response, f, is defined as the fraction of active receptors, [R]Active/[R]T (Appendix 1). (B) Simulation with the two-state model of agonism (Equation 1). A basal response, which depends on the L-value, is inherent to the model and ligands are agonists, neutral antagonists or inverse agonists if they increase, not change or decrease the basal response (α greater, equal or lower than 1, respectively). Concentration-effect curves for full agonist (α = 103), partial agonist (α = 10), neutral antagonist (α = 1), partial inverse agonist (α = 10−1) and full inverse agonist (α = 10−3). Fixed parameters: K = 10−6 and L = 0.5.