MONOAMINE OXIDASE INHIBITORY EFFECTS OF SOME 4-AMINOPHENETHYLAMINE DERIV ATIVES
The in vitra and ex viva monoamine oxidase (MAO) inhibitory effects of (±)4-dimethylaminoa- methyl-phenethylamine (4-DMAA) and (± )4-methylamino-a-methyl-phenethylamine (4-MAA) were reassessed, in comparison with the previously unstudied achiral parent compound, 4-dimethylaminophenethylamine (4-DMAPEA) and with a salt of 4-DMAA enriched in the levo isomer, ("-")4- DMAA, using amiftamine [5-(+)-4-dimethylamino-a,2-dimethylphenethylamine] as positive control. The in vitra studies confirmed that 4-amino-a-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 viva resuIts, in which catecholamines, serotonin (5-HT) and their metabolites were measured in two brain regions after i.p. administration, confirmed the results obtained in vitra. These results are consistent with the suggestion that the 4-amino group contributes toMAO inhibitory effects of a-methyl-phenethylamines, and show that the presence and orientation of an amethyl side chain substituent may be important when determining the potency and selectivity of these compounds. AlI compounds tested could be quantified by HPLC with electrochemical detection.
This work was partially supported by IPICS (International Program in the Chemical Sciences, Sweden), PEDECIBA (Programa de Desarrollo de las Ciencias Básicas, Uruguay) and FONDECYT (Grant No. 89-915,Chile).
Quote Item8ioch,mica/ Pharmacology, Vol. 47, No. 8, pp. 1365-1371, 1994