NATURALLY-OCCURRING ISOQUINOLINES PERTURB MONOAMINE METABOLISM IN THEBRAIN - STUDIED BY IN-VIVO MICRODIALYSIS

Naturally occurring isoquinolines affected the monoamine metabolism in the rat striatum, as proved by in vivo microdialysis technique. By an alysis of monoamines and their metabolites in the dialysate, dopamine- derived 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines were found to in hibit monoamine oxidase and catechol-O-methyltransferase activity. 1-M ethyl- and ethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline were fou nd to inhibit activity of type A monoamine oxidase most markedly. To c ompare the structure-activity relationship, corresponding isoquinoline s without a catechol structure were also examined. The inhibition by c atechol isoquinolines was more manifest than those without a catechol structure. Among latter isoquinolines, N-methyl-isoquinolinium ion was the most potent inhibitor of monoamine oxidase. In addition, catechol isoquinolines increased monoamine levels in the brain. The number and the site of the methyl group are essentially required for the inhibit ion of monoamine oxidase and a catechol structure for that of catechol -O-methyl-transferase. These results are discussed in relation to poss ible involvement of these isoquinolines to the clinical features of so me neuro-psychiatric diseases, such as alcoholism or in L-DOPA therapy .