PHARM/PCS V5 · Procedure 15 Receptor Pharmacology
pA2 Analysis I: Schild Plot
Estimate a competitive antagonist's pA2 from dose ratios at several antagonist concentrations, with the slope test that checks the competitive model.
What it computes
Determines the pA2 (affinity) of a competitive antagonist from a Schild plot: log(A′/A − 1) vs. −log[B]. Regression analysis yields the slope (theoretically −1), the pA2 (x-intercept), and their standard errors and confidence limits.
Inputs and outputs
You provide
- Antagonist concentration [B] and the agonist dose ratio A′/A, one pair per line
- A confidence level
PHARM/PCS reports
- Slope of the Schild line, with standard error and confidence limits
- pA2 from the x-intercept, with confidence limits
- Correlation coefficient
- The Schild plot with the fitted regression line
When to use it
When you have agonist dose-response curves measured at several antagonist concentrations and want to quantify the antagonist's affinity and confirm that its action is simple competitive antagonism, the standard route for characterizing an antagonist and helping classify the receptor it acts on.
Reading the results
A slope statistically indistinguishable from −1 is your evidence that the antagonism is simple and competitive; when it holds, the pA2 equals the pKB, a true affinity constant. A slope meaningfully steeper or shallower than −1 warns the model is being violated (a second receptor population, saturable removal of antagonist, or non-equilibrium conditions), and the pA2 should then be reported with caution. More antagonist concentrations anchor the regression; two points define a line but can't reveal curvature. For the time-based and slope-constrained variants, see Procedures 16 and 17.
The slope is the test
Confidence limits are reported on the slope as well as the pA2, so you can judge whether the slope is consistent with the theoretical −1. When it is, the pA2 equals pKB, a true affinity constant.
This page describes the procedure. Calculations run inside the licensed PHARM/PCS V5 application. PHARM/PCS is a trademark of MCS Scientific LLC.