(+)-4-Dimethylamino-2,alpha-dimethylphenethylamine (FLA 336(+)), a selective inhibitor of the A form of monoamine oxidase in the rat brain.
(+)-4-Dimethylamino-2,alpha-dimethylphenethylamine (FLA 336(+)) and its N-demethylated secondary amino derivative FLA 788(+) were examined for their monoamine oxidase (MAO) inhibitory effects in the rat brain. They were found to be reversible and very selective inhibitors of the A form  of monoamine oxidase in vitro and in vivo after oral administration. FLA 788(+) was 2-6 times more active than FLA 336(+) in vitro depending on the assay technique employed but the two compounds had similar potency after oral administration. Both compounds inhibited competitively the deamination of 5-hydroxytryptamine by hypothalamic mitochondria. Although the irreversible inhibitor clorgyline was 60 times more potent than FLA 336(+) in vitro, it was equipotent with FLA 336(+) and FLA 788(+) in the rat brain after oral administration. There was a high correlation between the log plasma concentration of FLA 788(+) and the MAO inhibition in hypothalamic slices. The plasma concentration of the metabolite FLA 788(+) exceeded that of FLA 336(+) after oral administration of the latter compound. Thus, the MAO inhibition produced by FLA 336(+) in vivo, appears in part to be due to the metabolite FLA 788(+).
D000818:Animals; D001921:Brain / Q000201:enzymology*; D007031:Hypothalamus / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008928:Mitochondria / Q000201:enzymology; D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism
D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; D012701:Serotonin; C034683:4-methylamino-alpha,2-dimethylphenethylamine; C031466:amiflamine