Hydroxyindole-O-methyltransferase V: Effects of Substituents on Hydrolysis of N-Acyltryptamines in Rats

The effects of substituents on the hydrolysis of the amide linkage were studied in rats with five tritium-labeled, substituted N-benzoyltryptamines and N-phenylacetyltryptamines. In the blood, amides of phenylacetic acid were hydrolyzed at a faster rate than those of benzoic acid. Methylation of the amide nitrogen facilitated hydrolysis rather than retarding it. These five inhibitors of hydroxyindole-O-methyltransferase accumulated in pineal glands 15 min. after intravenous injection. Substitution of the chlorine atom on 3-and 4-positions of the phenyl ring decreased the transport into the pineal glands but retarded the metabolism in the organ. Of the compounds studied, N-phenylacetyltryptamine demonstrated the longest duration in the rat pineal gland.