AN INVESTIGATION OF THE TOXICITY AND HYPOGLYCEMIC EFFECT OF SEVERAL GUANIDINE COMPOUNDS

¹ The Department of Biological Chemistry, Long Island College of Medicine, Brooklyn, New York

By comparing the results of these experiments, it becomes obvious that the respective actions of benzothiazole and benzoselenazo guanidine on blood sugar levels are similar. Their action upon the nitrogenous constituents indicate the selenazo compound to have greater activity. This fact is apparently contradicted, by a study of the toxicities of the respective compounds. This variation is readily explained, by the lesser solubility, with consequential lowered absorption of the selenium compound. Table 2 shows these facts, together with a summary of actions of the biguanides.

The compounds, a-m-tolyl biguanide and a-o-tolyl biguanide, are the least toxic members of this series; a-3-6-dimethylphenyl-biguanide is considerably more deadly. The most toxic biguanide studied was the diphenyl compound.

From these results one must conclude, this type of guanidine compound to be non-productive of hypoglycemia. It is also apparent that the order of toxicity increases directly with the number of benzene rings, and with the number of methyl groups.

[See table in the PDF file]

The relative position of the methyl group is shown to be unimportant as far as biological activity is concerned.

Reference to the conclusions of previous workers, indicates this deduction concerning the number of benzene rings to be substantially correct. The other findings are not corroborated.

The search for an insulin substitute for which this investigation was instigated was unfruitful. The following results, however, are worthy of mention:

1. The toxic dose of several compounds has been established.

2. Further data on the effect of structure on glycemic and toxic action is recorded.

3. The summary of normal blood values on fasting rabbits (table 3) is of interest to the animal experimenter.