N-substituted cyclopropylamines as inhibitors of MAO-A and -B forms

Monoamine oxidase (MAO) activity in mouse neuroblastoma homogenates was preferentially inhibited by N[2-(o-chlorophenoxy)-ethyl]cyclopropylamine (L-51641) and a series of structurally related compounds. Two other congeners (L-54761 and L-54748) from this series, however, demonstrated preferential inhibition of MAO in human platelet homogenates. As neuroblastoma and human platelet cells have been identified as possessing apparently exclusive MAO-A and MAO-B characteristics, respectively, L-54761 and L-54748 appear to be preferential MAO-B inhibitors. In keeping with this conclusion, a greater proportional inhibition of phenylethylamine oxidation than serotonin oxidation by these two compounds was found in rat brain homogenates, while contrasting results were obtained with L-51641. Preferential effects of L-54761 and L-51641 on phenylethylamine oxidation and, to a lesser extent, on serotonin oxidation were also observed in vivo.