schild analysis

Schild analysis is a classic pharmacology method for measuring how strongly a competitive antagonist blocks a receptor, and it works by watching how the antagonist pushes an agonist's dose–response curve around. The key trick is simple: a competitive antagonist does not lower the agonist's maximal effect; it just makes you use more agonist to get there, so its curve slides to the right. The more antagonist present, the further right the curve slides.

By measuring how far the curve shifts at several antagonist concentrations and plotting those shifts in a particular way (the Schild plot), one extracts a single number, the pA2 — essentially the negative logarithm of the antagonist concentration that forces you to double the agonist dose. A higher pA2 means a more potent antagonist. The procedure also serves as a diagnostic: if the plot comes out as a straight line of slope one, the antagonism is behaving as simple, reversible and competitive; a different slope or a curved line warns that something else is going on (the antagonist may be non-competitive, slowly reversible, or acting elsewhere).

Its strength is that pA2 measures the antagonist's affinity for the receptor in a way that does not depend on which agonist you used or on the tissue's amplification — a property of the antagonist itself. Its limits are equally honest: the analysis assumes the antagonism really is competitive and at equilibrium, so for slow-binding or insurmountable antagonists the classic Schild treatment breaks down and must be modified.