In our research, we have investigated the pharmacodynamic activity of a series of substances in terms of the physiopathological concepts discussed above: the level of organization at which they act, the dualistic nature of their activity, their relationship to body constituents, especially to lipids, and the changes they induce in the defense mechanism. We will limit ourselves in this presentation only to those of the substances investigated which are of therapeutic interest.

The dualistic concept has permitted didactic separation of agents into two groups with antagonistic properties. In the last analysis, this separation could be related to the two fundamental tendencies in nature, homotropy or heterotropy. For inorganic agents, this criterion appears to be directly related to the elements present. However, for organic agents, especially for lipids and lipid like substances, this simple criterion is less valid. Another, the positive and negative electrical character of their active polar groups could be used. It must be emphasized, however, that some of these polar groups show either positive or negative properties depending upon the medium in which they work. An alcohol, for example, can act as an acid under special circumstances, in which case it forms metal alcoholates; or it can act as an alcohol forming esters with acids. For this reason, in considering these substances, we have limited the sphere of changes studied to those corresponding to the conditions present in biological entities.

Since, as seen above, substances with negative polar groups actively intervene in various processes, while those with positive polar groups control the activity of the first, we will start this presentation with the former.

Agents With Active Negative Polar Groups

Among agents which have negative polar groups, a further division can be made according to the nature of these groups. Under biological conditions, the most important of negative polar groups is the carboxyl. Losing a proton when dissociated, the carboxyl confers acidic property to the molecule into whose structure it enters. We will consider, first, such car boxylic acids. Among such agents, the individual differences seen in biological activities have to be related to their nonpolar parts.

In the frame of our research, with organic acids, we were especially interested in those with a predominance of the nonpolar group; that is, those having lipoidic properties. They are, principally, fatty acids, which, according to the presence of one or more double or triple bonds in the nonpolar part, can be separated into saturated and unsaturated.