This is the first of a set of three papers in the Journal that were to transform the study of drug antagonism (see also Schild, 1949, and Arunlakshana & Schild, 1959). At the time it was written, there was a pressing need for methods that would allow the effectiveness of drugs to be measured and expressed in a consistent and reproducible fashion. As Schild noted in his introduction, the requirement was particularly great for antagonists because of the multiplicity of methods then used and the lack of information about their reproducibility. In this important paper he proposed and validated a new measure of antagonist action, pA. The key principle is that the same sub-maximal response to an agonist is measured first in the absence of antagonist and then in its presence, using a greater concentration of agonist. This was an important departure from early attempts to quantitate drug antagonism by determining the reduction that the antagonist caused in the response to a standard application of agonist. The results of such measurements had proved rather irreproducible, not only from laboratory to laboratory but even between different preparations of the same tissue.
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