Mode of action and characteristics of monoamine oxidase-A inhibition by moclobemide.
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.
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Pharmaceutical Research Department, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Kettler
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Imhof
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Da Prada
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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
D001549:Benzamides; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase; D020912:Moclobemide; D014439:Tyramine