Selective inhibition of the A form of monoamine oxidase by 4-dimethylamino-alpha-methylphenylalkylamine derivatives in the rat.
The inhibitory effects on monoamine oxidase (MAO) of some dimethylamino-alpha-phenylalkylamine derivatives were examined in a rat brain mitochondrial preparation in vitro and in rat brain slices following oral administration. In the in vitro assay the compounds were shown to be selective inhibitors of the A form of MAO, being 100-600 times more potent in inhibiting the deamination of [14C]5-hydroxytryptamine than that of [14C]phenetylamine. Using an ex vivo brain slice technique it was found that the new compounds were reversible and very selective inhibitors of type A MAO in the rat brain and the most potent compounds (FLA 405, 314, 336 and 558) were equipotent with clorgyline. The compounds increased the monoamine concentrations in whole rat brain, particularly that of 5-hydroxytryptamine, in the same dose range which produced MAO inhibition. Some of the new compounds, e.g. FLA 336 and FLA 717, caused only weak potentiation of the vaso-pressor effect of orally administered tyramine.
D000818:Animals; D046508:Culture Techniques; D003641:Deamination; D004298:Dopamine / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D010627:Phenethylamines / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D013329:Structure-Activity Relationship; D014439:Tyramine / Q000378:metabolism
D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; D012701:Serotonin; D008995:Monoamine Oxidase; D004298:Dopamine; D009638:Norepinephrine; D014439:Tyramine