title: MDL 72,974: a potent and selective enzyme-activated irreversible inhibitor of monoamine oxidase type B with potential for use in Parkinson's disease.
abstract: MDL 72,974, (E)-2-(4-fluorophenethyl)-3-fluoroallylamine, was designed to be a selective inhibitor of monoamine oxidase type B (MAO-B). In vitro, the compound inhibits rat brain mitochondrial MAO in a concentration and time-dependent fashion and shows marked selectivity for the B form (IC50 = 680 and 3.6 nM for MAO-A and MAO-B, respectively). After oral administration to rats, the compound shows preferential inhibition of brain MAO-B with ED50 values of 8 and 0.18 mg/kg p.o. for the A and B forms, respectively. Selectivity is retained on repeat dosing. MDL 72,974 did not significantly potentiate the cardiovascular effects of intraduodenually-administered tyramine in anaesthetized rats and had only minor indirect sympathomimatic effects in the pithed rat. At MAO-B selective doses the neurotoxic effect of MPTP in mice was blocked.
authors.affiliation: Merrell Dow Research Institute, Strasbourg, France.
authors.forename: M
authors.initials: M
authors.lastname: Zreika
authors.forename: J R
authors.initials: JR
authors.lastname: Fozard
authors.forename: M W
authors.initials: MW
authors.lastname: Dudley
authors.forename: P
authors.initials: P
authors.lastname: Bey
authors.forename: I A
authors.initials: IA
authors.lastname: McDonald
authors.forename: M G
authors.initials: MG
authors.lastname: Palfreyman
mesh_terms: D000284:Administration, Oral; D000498:Allyl Compounds; D000818:Animals; D002082:Butylamines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D020267:MPTP Poisoning; D008297:Male; D051379:Mice; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000498:Allyl Compounds; D002082:Butylamines; D008996:Monoamine Oxidase Inhibitors; C058000:mofegiline; D008995:Monoamine Oxidase