Schild analysis is used to determine the nature of antagonists to its receptor. Schild plots also give information on the potency of competitive antagonists and can hint at the presence of multiple binding sites. Information on whether the antagonist molecule binds with some form of cooperativity can also be inferred. The Schild equation is;
Schild Equation:
(conc. ratio - 1) = (antagonist conc.) / KB
Conc. ratio = Conc. of agonist producing a defined response in the presence of an antagonist, divided by the concentration producing the same response in the absence of the antagonist. So antagonist EC50 / agonist EC50.
KB = dissociation equilibrium constant for the antagonist
From the Schild plot a value known as the pA2 can be found. The pA2 is the negative logarithm of the concentration of antagonist, which would produce a 2-fold shift in the concentration response curve for an agonist, and is a logarithmic measure of the potency of an antagonist.
The pA scale is useful as it performs as an empirical measure of antagonist potency, which theoretically could characterise activity, specificity, and time-action relationships. This scale allowed scientists to present findings empirically instead of describing their results as "very sensitive". The pA2 is calculated by extrapolating the value on the x-axis when y=0.
![]()
So in this example the pA2 is 6.
The slope of the Schild plot gives information about the nature of the antagonist i.e. whether or not it is competitive binding and information on the cooperativity. The steepness of slope depends upon both the equilibration time and the degree of antagonism.
When the slope of the Schild plot is not 1 a number of possibilities arise: (1) the antagonist is not competitive, (2) a multimolecular interaction between drugs and receptors is being observed, (3) equilibrium conditions have not been attained in the experimental procedure.
The third condition is important as dynamic equilibrium in contrast to true equilibrium conditions may distort the nature of the antagonism; i.e. a competitive antagonist could appear to be non-competitive. This could occur in isolated tissues, which possess uptake and/or degradative mechanisms for either the agonist or antagonist.
When the Schild slope is equal to 1 this indicates that the antagonism is competitive and reversible. It also indicates that the agonist is acting at a single receptor subtype, and that the tissue has no uptake mechanism for the agonist. It can also be concluded that the antagonist causes a parallel rightward shift of the log agonist concentration response curve with no loss of maximal response.