Schild Analysis
Also known as: Schild plot, pA2
Schild analysis is a quantitative method for characterizing competitive receptor antagonism developed by Henry Schild in 1947. It uses dose-response curves in the presence and absence of antagonist to estimate the antagonist affinity constant (pA2), enabling standardized comparison of antagonist potency across drugs and experimental systems.
Key highlights
- Provides a single quantitative measure (pA2) for rapid comparison of antagonist potency
- Based on sound theoretical foundation of competitive antagonism; results are widely interpretable across labs
- Schild slope value (ideally = 1) validates mechanistic assumptions and identifies non-competitive antagonism
- Relatively simple to conduct using standard dose-response curve methodology
Intuition
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How it works
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When to use it
Use Schild analysis to characterize antagonist potency in isolated tissue preparations, receptor binding assays, or functional studies. It is standard in pharmacology for comparing new antagonists to reference compounds and for mechanistic classification of antagonism.
Strengths & limitations
- Provides a single quantitative measure (pA2) for rapid comparison of antagonist potency
- Based on sound theoretical foundation of competitive antagonism; results are widely interpretable across labs
- Schild slope value (ideally = 1) validates mechanistic assumptions and identifies non-competitive antagonism
- Relatively simple to conduct using standard dose-response curve methodology
- Assumes competitive antagonism; non-competitive antagonism violates assumptions and produces inaccurate pA2 values
- Requires multiple dose-response curves at different antagonist concentrations, increasing experimental workload
- pA2 is dependent on agonist choice; different agonists can yield different pA2 values for the same antagonist
- Does not directly measure receptor affinity; pA2 is a functional parameter influenced by efficacy and tissue properties
Common pitfalls
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Applications
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Frequently asked
What is pA2 and what does a higher value mean?
pA2 is -log(molar concentration of antagonist required to produce a two-fold rightward shift of the agonist dose-response curve). Higher pA2 indicates stronger antagonism (lower antagonist concentration required). A pA2 of 7 means an antagonist concentration of 10^-7 M produces a two-fold shift.
What does a Schild slope of 1 indicate?
A slope of 1 confirms purely competitive antagonism and validates the pA2 as a reliable antagonist affinity measure. A slope significantly different from 1 suggests non-competitive antagonism or allosteric effects, and pA2 becomes less interpretable as a simple affinity constant.
Can I compare pA2 values from different tissues or agonists?
Direct comparison is problematic because pA2 depends on agonist efficacy and tissue properties. However, pA2 values within the same experimental system (same tissue, same agonist) provide reliable relative potency ordering of antagonists.
What is the difference between pA2 and pKi?
pA2 is a functional estimate based on dose-response shifts. pKi is the dissociation constant from binding assays. Both reflect antagonist affinity but are measured by different methods; pA2 is easier in functional assays while pKi requires direct binding measurements.
Sources
- 1.Schild, H. O. (1947). pA, a new scale for the measurement of drug antagonism. Journal of Physiology, 106(3), 337-357.
- 2.Arunlakshana, O., & Schild, H. O. (1959). Some quantitative uses of drug antagonisms. British Journal of Pharmacology and Chemotherapy, 14(1), 48-58.
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Cite this page
ScholarGate. (2026, June 3). Schild Analysis. ScholarGate. https://scholargate.app/pharmacology/schild-analysis