Molecular Pharmacology, Vol 19, 367-371, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

Mathematical Analysis of the Kinetics of Competitive Inhibition in Neurotransmitter Receptor Binding Assays

¹ Departments of Pharmacology, Psychiatry, and Internal Medicine, University of Arizona Health Sciences Center, Tucson, Arizona 85724

The kinetics of competitive inhibition was described by first-order differential equations, and the solution to these equations was derived numerically. The results of this analysis showed that the IC₅₀ of a competitive inhibition curve decreases as equilibrium is approached if the dissociation rate constant of the nonlabeled ligand is equal to or less than that of the labeled ligand. The converse was true for competitive inhibition curves of a nonlabeled inhibitor with a dissociation rate constant greater than that of the labeled ligand. Nonequilibrium competitive inhibition experiments were performed using the muscarinic antagonist and agonist ligands, [³H]quinuclidinyl benzilate and [³H]cis-methyldioxolane, and results consistent with the theoretical predictions were observed.

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ACKNOWLEDGMENTS The authors wish to thank Susan Yamamura for her expert appraisal of the manuscript. We also acknowledge the expert technical assistance of David Chapman and the excellent secretarial assistance of Cathleen Thomas and Isabelle Preiss.