Monoamine oxidase inhibitory effects of some 4-aminophenethylamine derivatives

Abstract

The in vitro and ex vivo monoamine oxidase (MAO) inhibitory effects of (±)4-dimethylamino-α-methyl-phenethylamine 4-DMAA) and (±)4-methylamino-α-methyl-phenethylamine (4-MAA) were reassessed, in comparison with the previously unstudied achiral parent compound, 4-dimethyl-aminophenethylamine (4-DMAPEA) and with a salt of 4-DMAA enriched in the levo isomer, (“−”)-4-DMAA, using amiflamine [ S-(+)-4-dimethylamino- α,2-dimethylphenethylamine] as positive control. The in vitro studies confirmed that 4-amino-α-methylphenethylamine derivatives are highly selective and reversible MAO-A inhibitors. Furthermore, (“−”)-4DMAA was less active than the racemic mixture. The side chain-unsubstituted compound, 4-DMAPEA, proved to be a nonselective and reversible MAO inhibitor. The ex vivo results, in which catecholamines, serotonin (5-HT) and their metabolites were measured in two brain regions after i.p. administration, confirmed the results obtained in vitro. These results are consistent with the suggestion that the 4-amino group contributes to MAO inhibitory effects of α-methyl-phenethylamines, and show that the presence and orientation of an α-methyl side chain substituent may be important when determining the potency and selectivity of these compounds. All compounds tested could be quantified by HPLC with electrochemical detection.