The mass action equation in pharmacology.
The mass action equation is the building block from which all models of drug-receptor interaction are built. In the simplest case, the equation predicts a sigmoidal relationship between the amount of drug-receptor complex and the logarithm of the concentration of drug. The form of this function is also the same as most dose-response relationships in pharmacology (such as enzyme inhibition and the protein binding of drugs) but the potency term in dose-response relationships very often differs in meaning from the similar term in the simple mass action relationship. This is because (i) most pharmacological systems are collections of mass action reactions in series and/or in parallel and (ii) the important assumptions in the mass action reaction are violated in complex pharmacological systems. In some systems, the affinity of the receptor R for some ligand A is modified by interaction of the receptor with the allosteric ligand B and concomitantly the affinity of the receptor for ligand B is modified to the same degree. When this occurs, the observed affinity of the ligand A for the receptor will depend on both the concentration of the co-binding allosteric ligand and its nature. The relationships between drug potency in pharmacological models and the equilibrium dissociation constants defined in single mass action reactions are discussed. More detailed knowledge of efficacy has led to new models of drug action that depend on the relative probabilities of different states, and these have taken knowledge of drug-receptor interactions beyond Guldberg and Waage.
Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Terry
T
Kenakin
D000494:Allosteric Regulation; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008024:Ligands; D010600:Pharmacology; D011336:Probability; D011487:Protein Conformation; D011955:Receptors, Drug / Q000737:chemistry*
D008024:Ligands; D011955:Receptors, Drug
dose-response; mass action; pharmacology; receptor