By plotting values of pK a1 and pK a2 , the dissociation constants of the phenolic (pK a1 ) and amino (pK a1 ) group of the sympathomimetic amines, against the logarithm of the biological activity, a functional relationship having a broad maximum suggests itself. Additional active compounds at intermediate pK a ranges, chemically related to the sympathomimetic amines, are needed to substantiate this. Similar plots for the oxidative action of the enzyme amine oxidase on these compounds yield different types of functions, one apparently linear for pK a1 , and the other approximating a broadly concave downward curve for pK a1 . Different sites of chemical action presumably are involved for oxidation, as contrasted to pharmacological activity. It is not to be inferred from the foregoing that the role of chemical structure is minimized. Its intent is to reassert the importance of ionization, as a molecular characteristic, in elaborating biological effects, both facets requiring examination in the elucidation of the mechanism of action of any given series of compounds. Analogously, the strength of organic acids and bases, as indicated by their dissociation constants, is altered by substituents in the organic molecule. The scatter of the points is interpreted to indicate the degree to which structure over-rides ionization in the manifestation of biological effect, as well as some degree of experimental indeterminacy. The net effect of a compound will be determined by the interplay between structure and physico-chemical characteristics ( Albert, 1960).