title: Have many estimates of efficacy and affinity been misled? Revisiting the operational model of agonism.
abstract: 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.
authors.affiliation: Laboratory of Molecular Neuropharmacology and Bioinformatics, Institut de Neurociències and Unitat de Bioestadística, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Roche
authors.affiliation: Division of Pharmacology, Cluster Systems Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, Leiden, The Netherlands; Certara, Simcyp QSP, Canterbury Innovation Centre, Canterbury CT2 7FG, UK.
authors.forename: Piet H
authors.initials: PH
authors.lastname: van der Graaf
authors.affiliation: Laboratory of Molecular Neuropharmacology and Bioinformatics, Institut de Neurociències and Unitat de Bioestadística, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain. Electronic address: Jesus.Giraldo@uab.es.
authors.forename: Jesús
authors.initials: J
authors.lastname: Giraldo
mesh_terms: D004305:Dose-Response Relationship, Drug; D054313:Drug Agonism; D008954:Models, Biological