Developments of computer-based estimation of pA2 values and associated analysis

Abstract

The standard statistical-computing package GLIM is used to analyze data from agonist-antagonist studies for the estimation of the dissociation constant of the antagonist. The method follows the general approach of D.R. Waud (Analysis of dose-response curves. In Methods in Pharmacology, vol. 3, Smooth Muscle, ed. by E.E. Daniel and M. Paton, Plenum Press, New York, 1975) in employing an iterative nonlinear least-squares curve-fitting procedure. However, it differs in two important respects: 1) it is interactive; and 2) it allows linear adjustments for covariates and experimental design variables. This paper develops develops an alternative useful formulation of departure from simple competitivity and also a graphical display called a "Clark plot" showing how the spacings of the dose-response lines fit the theory of simple competitive antagonism. This plot provides an alternative to the popular Schild plot for which, of necessity, the zero antagonist (control) dose-response line is heavily used both in the experimental design and in the analysis associated with it.