PerspectiveFeatureHave many estimates of efficacy and affinity been misled? Revisiting the operational model of agonism

- The operational model with the slope parameter equal to 1 is a Hill equation.
- The operational model with the slope parameter different from 1 is not a Hill equation.
- Fitting the operational model to steep or flat Hill curves could yield misled parameter estimates.
- A new operational model is proposed to fit steep or flat Hill curves.

The operational model of agonism offers a general equation to account for steep or flat functional curves by including a slope parameter different from 1. However, because this equation is not a Hill equation, those steep or flat experimental curves that follow the Hill model are excluded from the operational framework. This conceptual omission could have significant consequences in the estimation of affinity and efficacy - the operational model tends to overestimate agonist-receptor dissociation constants and operational efficacy parameters to accommodate the shape of theoretical curves to steep or flat experimental Hill curves. To avoid misled parameter estimates for an ample space of pharmacological data a new version of the operational model has been developed.