This section is from the book "Research In Physiopathology As Basis Of Guided Chemotherapy With Special Application To Cancer", by Emanuel Revici. Also available from amazon: Research In Physiopathology
Theoretically, it was to be expected that lipids with an amine as polar group would have a marked anti fatty acid action. We studied several of these substances from the standpoint of their influence upon physiopatho logical changes considered related to lipoidic predominance. The first lipoid of the aliphatic amine series is hexylamine. A nonpolar group of at least 6 carbons is required for predominance over the potent amino radical. From commercial sources, we obtained amines corresponding to the usual saturated fatty acids with even numbers of carbons, ranging from 6 to 18; a few unsaturated with 18 carbons; and heptylamine with an odd number of carbons. All these compounds, when injected in mice and rats produced severe local reactions, often followed by skin ulcerations, even when administered in oily solutions. For this reason, we tried salts of these amines usually obtained with acetic or hydrochloric acid. Salts of the lower members of the series, no longer had lipoidic character. However, we could use hexylamine in an oily solution for intramuscular injection. It appeared to be relatively well tolerated locally even in humans. No apparent changes were seen, however, in systemic analyses, and the immediate and long range effects upon pain were minimal. No changes were obtained in experimental tumors except by local treatment, as in ascites tumor, or by injecting the product at the level of the transplant itself, in which case the growth of the tumor was slowed or even halted. A similar effect was seen when the transplant was dipped in the oily solution of the product and the procedure was repeated in successive generations.
On a larger scale, we utilized, both in animals and humans, the salt obtained from hexylamine with nicotinic acid. It showed favorable influence on pain of alkaline pattern, and exacerbated pain of acid pattern, but had no other effects. Heptylamine has been used by others as a hypertensive agent. In our studies, its hypertensive activity appeared to be weak and transitory.
The study of lipamines was the starting point for an entire series of researches into the biological role of the amino group, especially as it intervenes in a complex molecule. We have seen that, like all other polar groups, the amino group will act as a fixing group in a molecule. Its characteristics appear to be related to its capacity to bind the molecule to other molecules in a relatively stronger and more specific way than other polar groups.
The realization of more complex chemical polymers as biological entities evidently is related to this capacity of the amino group. This appears clear when the amino group is bound to various acids in the alpha position to form the alpha amino acids that enter into the formation of complex proteins. In amino sugars, the amino group shows the same property, producing the polymer formations characteristic of connective tissues. Furthermore, it is the amino group, acting as a second polar group, which gives to alkaline amino acids their fundamental role in the biological realm, as mentioned above. The alkaline amino acids, like other amino acids, form polymers through their amino acid group. However, as these polymers, histories or protamines remain reactive through the terminal alkaline nitrogen containing groups and it is through these groups that they realize new bonds, such as to nucleic acids.
In a molecule with two polar groups far apart the amino group will fix the molecule, while the other active radical will provide reactivity. The selective fixation upon certain constituents in various places in the organization accomplished by the amino group localizes the intervention of the other active groups of the molecule.
We have considered many of the biological substances containing an amino group and a second active group. Typical examples are the local anesthetics in which the amino group acts to fix the molecule, while the other energetic formations intervene more actively to induce the anaesthetic effect. Similarly, in epinephrine and ephedrine, the amino group serves to fix the molecule, while the hydroxyls later intervene more specifically.
In some molecules such as the alkaline amino acids, the second active group can be another amine or another nitrogen containing group. It was for this reason that we first became interested in investigating natural and synthetic compounds with an amino acid to serve for fixation, and another energetic center to intervene more actively. We studied amino butanols, but no particular activity could be found. These agents, however, were not lipoids. We were consequently interested in substances having a lipoid character as well as two active polar groups of which one is an amine. A study of these agents is now in progress.