SALSOLINOLS AND OTHER 6,7-DIHYDROXY-1,2,3,4-TETRAHYDROISOQUINOLINES AS INHIBITORS OF MONOAMINE-OXIDASE - IN-VIVO AND IN-VITRO STUDY

The effects of naturally occurring tetrahydroisoquinolines on monoamin e catabolism were examined by in vivo microdialysis study in the rat s triatum, or by in vitro experiments using human brain synaptosomes as enzyme samples. By in vivo experiment, catechol isoquinolines, (R) and (S) enantiomer of 1-methyl- and ethyl-6,7-dihydroxy-1,2,3,4-tetrahydr oisoquinoline (salsolinol and N-methyl-norsalsolinol) markedly inhibit ed oxidation of serotonin by type A oxidase. On the other band, isoqui nolines without catechol, 1,2,3,4-tetrabydroisoquinoline, 1-methyl-der ivative and N-methyl-isoquinolinium ion, mainly inhibited dopamine met abolism by the oxidase. By in vitro experiments, norsalsolinol and sal solinol, and their N-methylated derivatives were found to inhibit mono amine oxidase. N-Methyl-norsalsolinol, (R) and (S) enantiomer of salso linol, and N-methyl-salsolinols inhibited type A monoamine oxidase com petitively to the substrate, kynuramine, and R enantiomers were more p otent inhibitors than S enantiomers. The inhibition was reversible. No rsalsolinol induced positive cooperativity toward kynuramine. Both nor salsolinol and N-methyl-norsalsolinol inhibited type B oxidase non-com petitively to the substrate, but their K(i) values were much higher th an those to type A. These results are discussed in relation to possibl e involvement of the isoquinolines as neuro-toxic and neuro-protective agents to the pathogenesis of some neuro-degenerative diseases, such as Parkinson's disease, or to clinical features of some diseases, such as alcoholism.