Ferner 2016 Br J Clin Pharmacol

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Ferner RE, Aronson JK (2016) Cato Guldberg and Peter Waage, the history of the Law of Mass Action, and its relevance to clinical pharmacology. Br J Clin Pharmacol 81:52-5. doi:10.1111/bcp.12721.

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Ferner RE, Aronson JK (2016) Br J Clin Pharmacol

Abstract: We have traced the historical link between the Law of Mass Action and clinical pharmacology. The Law evolved from the work of the French chemist Claude Louis Berthollet, was first formulated by Cato Guldberg and Peter Waage in 1864 and later clarified by the Dutch chemist Jacobus van ‘t Hoff in 1877. It has profoundly influenced our qualitative and quantitative understanding of a number of physiological and pharmacological phenomena. According to the Law of Mass Action, the velocity of a chemical reaction depends on the concentrations of the reactants. At equilibrium the concentrations of the chemicals involved bear a constant relation to each other, described by the equilibrium constant, K. The Law of Mass Action is relevant to various physiological and pharmacological concepts, including concentration–effect curves, dose–response curves, and ligand–receptor binding curves, all of which are important in describing the pharmacological actions of medications, the Langmuir adsorption isotherm, which describes the binding of medications to proteins, activation curves for transmembrane ion transport, enzyme inhibition and the Henderson–Hasselbalch equation, which describes the relation between pH, as a measure of acidity and the concentrations of the contributory acids and bases. Guldberg and Waage recognized the importance of dynamic equilibrium, while others failed to do so. Their ideas, over 150 years old, are embedded in and still relevant to clinical pharmacology. Here we explain the ideas and in a subsequent paper show how they are relevant to understanding adverse drug reactions.

Bioblast editor: Gnaiger E


  • "The concept of ‘affinity’ as the chemical force that holds together dissimilar substances is ascribed to Herman Boerhaave (1668–1738), the influential Leiden physician and the author of Elementa chemiae. As he wrote: ‘…the dissolving and dissolved particles […] unite, by the affinity of their own nature, into homogeneous bodies’."
  • "The French chemist Claude Louis Berthollet (1748–1822) then considered the driving force behind chemical reactions and established the relation between the mass of a substance and the rate at which it undergoes a chemical reaction."
  • "It was not until 1864, however, that the Norwegian mathematician Cato Guldberg (1836–1902) and the chemist Peter Waage (1833–1900), Guldberg's brother‐in‐law, clearly propounded the Law of Mass Action. That their paper was neglected was perhaps foreseeable, since it was written in Norwegian."
  • "The fundamental ideas behind Guldberg and Waage's Law of Mass Action, namely that in an elementary reaction the rate depends on the concentrations of reactants and the stoichiometry of the reaction and that at equilibrium the products and reactants are in fixed ratio, have profoundly influenced pharmacology."

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Labels: MiParea: Pharmacology;toxicology 

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