Inhibition of monoamine oxidase by 3,4-dihydroxyphenyl 1-alanine and its analogs

Abstract

The mechanisms underlying the therapeutic action, the adverse side-effects, and the decline in efficacy upon prolonged administration of L-DOPA in patients with Parkinson's disease are not yet well understood. Therefore, further studies of the biochemical effects of L-DOPA are required. The current article indicates that L-DOPA, D-DOPA and L-alpha-methyl-DOPA can reversibly inhibit monoamine oxidase (MAO) activity. Inhibition of MAO-A of human placental mitochondria by L- and D-DOPA was non-competitive with the substrate kynuramine (Ki = 154 microM and 133 microM, respectively). L-alpha-methyl-DOPA competitively inhibited MAO-A (Ki = 121 microM). MAO-A and MAO-B of human liver mitochondria were also inhibited by L-DOPA (Ki = 152 microM and 275 microM, respectively). These results indicate that L-DOPA or L-alpha-methyl-DOPA might act, to some extent, by perturbing the catabolism of brain biogenic amines, but no direct evidence indicates that the brain concentrations of these drugs achieved during therapy are high enough to inhibit MAO activity.