Food-derived heterocyclic amines, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole and related amines, as inhibitors of monoamine metabolism.

The effects of heterocyclic amines, pyrolysis products of tryptophan, on monoamine metabolism were examined. Among these amines, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) are potent inhibitors of the enzymes related to amine metabolism. They inhibited type A monoamine oxidase more markedly than type B. After culture of a dopamine cell model, clonal pheochromocytoma PC12h cells, with Trp-P-1 activity of tyrosine hydroxylase was decreased by reduction of its affinity to the biopterin cofactor. Trp-P-1 and Trp-P-2 inhibited tryptophan hydroxylase competitively with the substrate and non-competitively with biopterin. These results suggest that food-derived heterocyclic amines may perturb the monoamine levels in the brain through the inhibition of the biosynthesis and metabolism of biogenic amines.