title: Inhibition of monoamine oxidase by N-methylisoquinolinium ion.
abstract: N-Methylisoquinolinium ion (N-MIQ) has been found to inhibit the biosynthesis of catecholamines; it inhibited tyrosine hydroxylase activity in striatal tissue slices. In this article, the effects of N-MIQ and an analogue, N-methylquinolinium ion, on monoamine oxidase (MAO) activity were examined to see their effects on the catabolism of catecholamines. MAO-A in human placental mitochondria was strongly inhibited by N-MIQ in competition with the substrate. The apparent Ki value of N-MIQ was found to be 20.4 +/- 1.1 microM, whereas that of N-methylquinolinium ion was 54.6 +/- 4.5 microM. MAO-B in human brain synaptosomes and liver mitochondria was found to be inhibited by N-MIQ, but the inhibition proved to be noncompetitive. The inhibition of MAO-B by N-MIQ was completely reversible by dialysis of the incubation mixture. MAO-A in human brain and liver mitochondria was more sensitive to the inhibitor than MAO-B. By quantitative analysis of N-MIQ, using HPLC, it was found not to be catabolized by the incubation with mitochondria, suggesting that the inhibition was due to N-MIQ itself and not due to any metabolic product. The inhibition of MAO by N-MIQ is discussed in terms of its possible involvement of the etiology of parkinsonism.
mesh_terms: D001921:Brain / Q000201:enzymology; D005260:Female; D006801:Humans; D008928:Mitochondria / Q000201:enzymology; D008930:Mitochondria, Liver / Q000201:enzymology; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D011806:Quinolinium Compounds / Q000494:pharmacology*; D013574:Synaptosomes / Q000201:enzymology
chemical_list: D008996:Monoamine Oxidase Inhibitors; D011806:Quinolinium Compounds; C051351:N-methylisoquinolinium