Monoamine oxidase inhibitory effects of some 4-aminophenethylamine derivatives.
The in vitro and ex vivo monoamine oxidase (MAO) inhibitory effects of (+/-)4-dimethylamino-alpha-methyl-phenethylamine (4-DMAA) and (+/-)4-methylamino-alpha-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-alpha,2-dimethylphenethylamine] as positive control. The in vitro studies confirmed that 4-amino-alpha-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 alpha-methyl-phenethylamines, and show that the presence and orientation of an alpha-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.
Reyes-Parada
M
M
Department of Chemistry, Faculty of Sciences, Universidad de Chile, Santiago.
Scorza
M C
MC
Silveira
R
R
Dajas
F
F
Costa
G
G
Tipton
K F
KF
Cassels
B K
BK
D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D009638:Norepinephrine / Q000032:analysis; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000032:analysis; D013237:Stereoisomerism
D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; C057324:2-(4-aminophenyl)ethylamine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; C031466:amiflamine; D009638:Norepinephrine