THE ACTION OF VARIOUS DRUGS ON CERTAIN PHASES OF IN VITRO ANABOLISM

¹ Department of Physiology and Pharmacology, Duke University School of Medicine, Durham, North Carolina

1. In a final concentration of 1 x 10^-3 M colchicine, methyl-bis-(beta-chloro-ethyl)-amine·HCl (MBA), and urethane inhibited the synthesis of creatine, the methylation of nicotanamide, and conjugation of p-aminobenzoic acid with glycine, of morphine with glucuronic acid, and of phenol with sulfuric acid to varying degrees.

2. MBA was a more generalized inhibitor than either colchicine or urethane. Where both colchicine and urethane were active, colchicine was more effective.

3. MBA markedly inhibited formation of urea from all sources. Urethane appeared to block the conversion of ornithine to arginine, and thus inhibit urea synthesis.

4. Urethane produced its greatest effect in the methylation processes. Where urethane was effective, a series of homologous carbamates exhibited essentially the same degree of activity, with one exception. Methyl carbamate was the least active.

5. From data with mutual inhibitors on two presumably similar methylation reactions (methylation of guanidoacetic acid and of nicotinamide) it is indicated that the two mechanisms involved may be similar.