title: Displacement of in vivo binding of [3H]brofaromine to rat intestinal monoamine oxidase A by orally administered tyramine.
abstract: The reversibility of the interaction of inhibitors with monoamine oxidase (MAO) is thought to provide a safety valve with respect to tyramine potentiation. We sought experimental evidence for this concept by studying the binding of orally administered [3H]brofaromine to the A-form of MAO in the rat ileum. Specific binding, defined by pretreatment with 10 mg/kg clorgyline p.o., amounted to 70-90% of total binding between 30 min and 6 h after administration of the radioligand. Brofaromine and clorgyline dose dependently displaced [3H]brofaromine with ED50 values of about 0.2 mg/kg when administered orally after the radioligand; so did orally administered tyramine in doses relevant for tyramine potentiation in the rat. It was also found that tyramine was relatively more effective in partially MAO-inhibited rats. The data suggest that the concept of reversibility functioning as a safety valve with respect to the potentially hazardous effects of tyramine ingestion is realistic.
authors.affiliation: Research Department, Pharmaceuticals Division, Ciba-Geigy Ltd., Basel, Switzerland.
authors.forename: P C
authors.initials: PC
authors.lastname: Waldmeier
authors.forename: K
authors.initials: K
authors.lastname: Stöcklin
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive; D003010:Clorgyline / Q000494:pharmacology; D004357:Drug Synergism; D007082:Ileum; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000378:metabolism*; D010880:Piperidines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D014439:Tyramine / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D008996:Monoamine Oxidase Inhibitors; D010880:Piperidines; C038213:brofaromine; D003010:Clorgyline; D014439:Tyramine