Naturally-occurring isoquinolines perturb monamine metabolism in the brain: studied by in vivo microdialysis

Abstract

Naturally occurring isoquinolines affected the monoamine metabolism in the rat striatum, as proved by in vivo microdialysis technique. By analysis of monoamines and their metabolites in the dialysate, dopamine-derived 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines were found to inhibit monoamine oxidase and catechol-O-methyltransferase activity. 1-Methyl- and 2-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline were found to inhibit activity of type A monoamine oxidase most markedly. To compare the structure-activity relationship, corresponding isoquinolines without a catechol structure were also examined. The inhibition by catechol 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 inhibition of monoamine oxidase and a catechol structure for that of catechol-O-methyl-transferase. These results are discussed in relation to possible involvement of these isoquinolines to the clinical features of some neuro-psychiatric diseases, such as alcoholism or in L-DOPA therapy.