Amiflamine is a selective and reversible inhibitor of monoamine oxidase (MAO) type A which exerts a preferential effect on serotonin (5-HT) catabolism. The (+)-enantiomer is the active stereoisomer. In a series of p-aminosubstituted phenethylamines, the ( + )-enantiomer of the compound amiflamine (4-dimethylamino-2-a-dimethylphenethylamine) was found to be a potent, selective, and reversible MAO type A inhibitor. Amiflamine (FLA 336(+] and its two metabolites, FLA 788(+) and FLA 668(+) were found to be competitive inhibitors of the activity of monoamine oxidase-A in homogenates of human hypothalamus and liver obtained at autopsy. Ki values, determined at pH 7.2, were 1.3, 0.3 and 22 uM (liver) and 0.8, 0.2 and 14 uM (hypothalamus) for amiflamine, FLA 788(+) and FLA 668(+), respectively. Monoamine oxidase-B activity was only weakly inhibited by the compounds. This initial phase I study in six normal subjects showed that the new MAO inhibitor amiflamine can be tolerated in single oral doses up to 80 mg without significant pharmacologic effects. Doses up to 60 mg were tolerated without any subjective or objective effects.