title: Inhibition of type A monoamine oxidase by methylquinolines and structurally related compounds.
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 microM, which was smaller than the Km value toward kynuramine, an amine substrate, 46.2 +/- 2.8 microM. 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.
authors.affiliation: Department of Biochemistry, Nagoya University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Naoi
authors.forename: T
authors.initials: T
authors.lastname: Nagatsu
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000201:enzymology; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000201:enzymology; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D006801:Humans; D008928:Mitochondria / Q000201:enzymology; D008930:Mitochondria, Liver / Q000201:enzymology; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010673:Pheochromocytoma / Q000201:enzymology; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000201:enzymology; D014407:Tumor Cells, Cultured
chemical_list: D008996:Monoamine Oxidase Inhibitors; D011804:Quinolines; D008995:Monoamine Oxidase