title: Mode of action and characteristics of monoamine oxidase-A inhibition by moclobemide.
abstract: The mode of interaction of the reversible monoamine oxidase-A (MAO-A) inhibitor moclobemide with the enzyme was investigated. The inhibition of rat brain or human placenta MAO-A by moclobemide showed an initial competitive phase, with a relatively low affinity (KI = 0.2-0.4 mM). However, the potency of the inhibitor was increased with incubation time. The time-dependent component of the association of moclobemide with MAO-A followed pseudo-first order kinetics. In contrast to mechanism-based inhibitors, no indication for adduct or product formation was detected after incubation of moclobemide with the enzyme. Even though some aspects of the moclobemide interaction with MAO-A are still not completely elucidated, this compound seems to have the characteristics of a slow-binding inhibitor.
authors.affiliation: Pharmaceutical Research Department, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: A M
authors.initials: AM
authors.lastname: Cesura
authors.forename: R
authors.initials: R
authors.lastname: Kettler
authors.forename: R
authors.initials: R
authors.lastname: Imhof
authors.forename: M
authors.initials: M
authors.lastname: Da Prada
mesh_terms: D001549:Benzamides / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D005260:Female; D006801:Humans; D007700:Kinetics; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D020912:Moclobemide; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D014439:Tyramine / Q000378:metabolism
chemical_list: D001549:Benzamides; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase; D020912:Moclobemide; D014439:Tyramine