4‐(O‐Benzylphenoxy)‐N‐Methylbutylamine (Bifemelane) and Other 4‐(O‐Benzylphenoxy)‐N‐Methylalkylamines as New Inhibitors of Type A and B Monoamine Oxidase

Abstract: 4‐( O ‐Benzylphenoxy)‐ N ‐methylbutylamine (Bifemelane, BP‐ N ‐methylbutylamine), a new psychotropic drug, was found to inhibit monoamine oxidase (MAO) in human brain synaptosomes. It inhibited type A MAO (MAO‐A) competitively and type B (MAO‐B) noncompetitively. BP‐ N ‐methylbutylamine had a much higher affinity to MAO‐A than an amine substrate, kynuramine, and it was a more potent inhibitor of MAO‐A than of MAO‐B. The K i values of MAO‐A and ‐B were determined to be 4.20 and 46.0 μ M , respectively, while the K m values of MAO‐A and ‐B with kynuramine were 44.1 and 90.0 μ M , respectively. The inhibition of MAO‐A and ‐B by BP‐ N ‐methylbutylamine was found to be reversible by dialysis of the incubation mixture. MAO‐A in human placental and liver mitochondria and in a rat clonal pheochromocytoma cell line, PC12h, was inhibited competitively by BP‐ N ‐methylbutylamine, while MAO‐B in human liver mitochondria was inhibited noncompetitively, as in human brain synaptosomes. BP‐ N ‐methylbutylamine was not oxidized by MAO‐A and ‐B. The effects of other BP‐ N ‐methylalkylamines, such as BP‐ N ‐methylethylamine, ‐propylamine, and ‐pentanylamine, on MAO activity were examined. BP‐ N ‐methylbutylamine was the most potent inhibitor of MAO‐A, and BP‐ N ‐methylethylamine and ‐propylamine inhibited MAO‐B competitively, whereas BP‐ N ‐methylbutylamine and ‐pentanylamine inhibited it noncompetitively. Inhibition of these BP‐ N ‐methylalkylamines on MAO‐A and ‐B is discussed in relation to their chemical structure.