Inhibition of Type A Monoamine Oxidase by Methylquinolines and Structurally Related Compounds

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Abstract
A series of methylquinolines (MQ) were found to inhibit markedly type A monoamine oxidase (MAO) in human brain synaptosomal mitochondria. 4‐MQ and 6‐MQ inhibited type A MAO (MAO‐A) competitively and 7‐ and 8‐MQ inhibited MAO‐A noncompetitively. Among these four isomers of MQ, 6‐MQ was the most potent inhibitor; the Ki value toward MAO‐A was 23.4 ± 1.8 μM, which was smaller than the Km value toward kynuramine, ± amine substrate, 46.2 ± 2.8 μM. On the other hand, MQ were very weak inhibitors of type B MAO (MAO‐B) and 8‐MQ did not inhibit MAO‐B in brain synaptosomal mitochondria. The inhibition of MAO‐A proved to be reversible; by dialysis the inhibition of MQ was completely reversible. The affinity of these isomers of MQ toward MAO‐A or ‐B was confirmed further with human liver mitochondria as sources of MAO‐A and ‐B and with human placental mitochondria and rat pheochromocytoma PC12h cell line as sources of MAO‐A. The relationship of the chemical structure of structurally related quinoline and isoquinoline derivatives to inhibition of the activity of type A or B MAO was examined.