title: Selective inhibition by amiflamine of monoamine oxidase type A in rat brain, liver and duodenum.
abstract: Amiflamine (FLA 336(+)), N-desmethylamiflamine (FLA 788(+)) and N,N-didesmethylamiflamine (FLA 668(+)) were examined for their monoamine oxidase (MAO) inhibitory effects in rat brain, liver and duodenum and were compared with the irreversible inhibitors clorgyline and (-)-deprenyl. The potency of each FLA compound was the same in each tissue both in vitro and after oral administration with either serotonin or tyramine as substrate. The in vitro effect of FLA 788(+) was 2-6 times stronger than that of amiflamine although the compounds were equipotent after oral administration. FLA 668(+) was 2-3 times less potent than amiflamine in vitro and had very poor activity after oral administration. The deamination of phenethylamine was weakly affected by the three FLA compounds. Clorgyline inhibited strongly the deamination of serotonin and tyramine in the duodenum after oral administration, being 1,000 times more potent than in the brain and the liver. Similar results were obtained for (-)-deprenyl which, however, was more potent in inhibiting the deamination of phenethylamine than that of serotonin and tyramine. Amiflamine was a reversible MAO inhibitor with no MAO inhibitory capacity 24 h after a single oral dose. On the other hand the irreversible inhibitor clorgyline had a maximal effect on brain MAO 48 h after a single dose while the inhibitory effect in the duodenum had almost disappeared. The influence of amiflamine on the excretion of acid and basic metabolites of orally administered 14C-tyramine (58 mumol/kg) in rat was examined.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology*; D003010:Clorgyline / Q000494:pharmacology; D003641:Deamination; D004386:Duodenum / Q000201:enzymology*; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology*; D008297:Male; D008928:Mitochondria / Q000201:enzymology; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010624:Phenelzine / Q000494:pharmacology; D010627:Phenethylamines / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D014439:Tyramine / Q000378:metabolism
chemical_list: D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; D012701:Serotonin; D003010:Clorgyline; C031466:amiflamine; D010624:Phenelzine; D014439:Tyramine