Carcinogenic Tryptophan Pyrolysis Products Potent Inhibitors of Type A Monoamine Oxidase and the Platelet Response to 5-Hydroxytryptamine

The effects of carcinogenic heterocyclic amines and -carbolines on 5-hydroxytryptamine-induced human platelet aggregation, on the uptake of 5-hydroxytryptamine by platelets, and on human monoamine oxidase activity were investigated. Of the dietary carcinogens and -carbolines studied, carcinogenic tryptophan pyrolysis products had greater pharmacological activities than other heterocyclic amines. The carcinogenic tryptophan pyrolysis products, 3-amino-l, 4-dimethyl-5H-pyrido[4, 3-b]indole and 3-amino-l-methyl-5H-pyrido[4, 3-b]indole, which have been identified in the dialysis fluid of uraemic patients, were the most potent inhibitors of the aggregation response to 5-hydroxytryptamine, with IC50 (the concentrations causing 50% inhibition) values of 10 μιηοΐ/ΐ and 50 μιηοΐ/ΐ, respectively. 3-Amino-l, 4-dimethyl-5H-pyrido[4, 3-b]indoleand 3-amino-l-methyl-5H-pyrido[4, 3-b]indole by themselves did not induce platelet aggregation, although these dietary carcinogens structurally resemble 54iydroxytryptamine. Kinetic analyses showed that 3-amino-l, 4-dimethyl-5H-pyrido[4, 3-b]indole and 3*amino-l-methyl-5H-pyrido[4, 3-b]indole were potent competitive inhibitors of 5-hydroxytryptamine uptake by platelets with /ζ 18 μπιοΐ/ΐ and 42 μιηοΐ/ΐ, respectively. Furthermore, carcinogenic tryptophan pyrolysates as well as -carbolines were found to be competitive selective inhibitors of monoamine oxidase ‘type A’.