EFFECT OF DRUGS ON THE TRYPTAMINE CONTENT OF RAT TISSUES

¹ Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland

The effect of drugs on the tryptamine content of rat organs was studied by means of an isotopic-enzymatic method. l-Tryptophan, iproniazid and p-chlorophenylalanine produced a moderate increase in the brain tryptamine concentration. The combined administration of the three drugs increased the brain tryptamine 7-fold. l-Tryptophan together with iproniazid also increased the tryptamine content in heart and lung. Lung tissue retained high tryptamine levels for a longer period. The decarboxylase inhibitors MK-486 and NSD-1055 antagonized the tryptamine increase produced by l-tryptophan plus iproniazid in peripheral tissues but failed to modify endogenous tryptamine levels. In the brain MK-486 (a peripheral decarboxylase inhibitor) administered i.p. increased endogenous tryptamine. NSD-1055, which also inhibits brain decarboxylase, produced a partial decrease in this amine. The administration of reserpine was without any effect in the brain and heart and only slightly decreased the endogenous tryptamine in lung. These results indicate that the decarboxylation of l-tryptophan to tryptamine is an alternate pathway for the tryptophan metabolism in rat tissues, especially after tryptophan hydroxylase inhibition and tryptophan administration. The normal presence of tryptamine in human brain also is reported.