The Hill equation and the origin of quantitative pharmacology |
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Authors: | Rudolf Gesztelyi Judit Zsuga Adam Kemeny-Beke Balazs Varga Bela Juhasz and Arpad Tosaki |
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Institution: | (1) Division of Cardiology, Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA |
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Abstract: | This review addresses the 100-year-old Hill equation (published in January 22, 1910), the first formula relating the result
of a reversible association (e.g., concentration of a complex, magnitude of an effect) to the variable concentration of one
of the associating substances (the other being present in a constant and relatively low concentration). In addition, the Hill
equation was the first (and is the simplest) quantitative receptor model in pharmacology. Although the Hill equation is an
empirical receptor model (its parameters have only physico-chemical meaning for a simple ligand binding reaction), it requires
only minor a priori knowledge about the mechanism of action for the investigated agonist to reliably fit concentration-response
curve data and to yield useful results (in contrast to most of the advanced receptor models). Thus, the Hill equation has
remained an important tool for physiological and pharmacological investigations including drug discovery, moreover it serves
as a theoretical basis for the development of new pharmacological models. |
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