INHIBITION OF MONOAMINE OXIDASE-A AND MONOAMINE OXIDASE-B BY SIMPLE ISOQUINOLINE ALKALOIDS - RACEMIC AND OPTICALLY-ACTIVE 1,2,3,4-TETRAHYDRO-ISOQUINOLINE, 3,4-DIHYDRO-ISOQUINOLINE, AND FULLY AROMATIC ISOQUINOLINE

A series of 1,2,3,4-tetrahydro-, 3,4-dihydro-, and fully aromatic isoquinolines were tested as substrates and/or inactivators of highly purified human monoamine oxidase A and B (MAO A and B). None were found to be a substrate for either enzyme, but many of these isoquinolines could selectively inhibit either MAO A or B. Stereoselective competitive inhibition of MAO A was found with the R enantiomer of all the stereoisomers tested, including salsolinol (Ki= 31 /µM), salsoline (Ki= 77 µM), salsolidine (Ki= 6 µM), and carnegine (Ki= 2 µM). As a class, the 3,4-dihydroisoquinolines were the most potent inhibitors tested (Ki= 2-130 µM), and the fully aromatic isoquinolines had intermediate activity (Ki= 17-130 µM) against MAO A. In contrast, only a few of these compounds markedly inhibited MAO B. 1,2,3,4-Tetrahydroisoquinoline, its 2-methyl derivative, and o-methylcorypalline gave apparent Kivalues of 15, 1, and 29 µM, respectively, and two 3,4-dihydroisoquinolines (compounds 22 and 25) showed substantial inhibition of MAO B (Ki= 76 and 15 µM, respectively). These results support the concept that the topography of the inhibitor binding site differs in MAO A and B. © 1990, American Chemical Society. All rights reserved.