Schild Regression Analysis

Quantitative pharmacological method determining whether an antagonist is competitive and measuring its equilibrium affinity constant (KB / pA2).

Specifications & Metrics

type: Receptor Theory & Kinetics
readout: Double-logarithmic plot of log10(dose ratio r − 1) versus log10[antagonist concentration B]
measures: Antagonist equilibrium dissociation constant (KB), empirical potency (pA2), and competitive surmountability
format: Parallel agonist concentration-response curves measured across multiple fixed antagonist concentrations
pioneer: Heinz Otto Schild (University College London, derived from the Gaddum competitive binding equation)

Named after pharmacologist Heinz Otto Schild, Schild analysis quantifies the parallel rightward shift that a surmountable competitive antagonist produces in an agonist concentration-response curve without depressing the maximal response.
For each antagonist concentration [B], the dose ratio (r) is calculated as the ratio of the agonist EC50 in the presence of antagonist to the control agonist EC50 in its absence, obeying the Schild equation r = 1 + [B]/KB.
Plotting log10(r − 1) against log10[B] yields a straight line with a slope of 1.0 for a true competitive antagonist; the x-intercept defines pA2 (−log10 KB), the negative logarithm of the molar antagonist concentration requiring a two-fold agonist dose increase.