Short-lasting and reversible inhibition of monoamine oxidase-A by moclobemide.
In ex vivo experiments, the time course of monoamine oxidase-A (MAO-A) inhibition after 10 mg/kg oral moclobemide was virtually the same for whole rat brains and liver: the onset was rapid, the maximum effect was obtained in 15 min, and the duration of action was short (about 16 h) compared with several days for the irreversible MAO inhibitors. The time course of MAO-B inhibition was peculiar: almost complete inhibition was obtained in the time only between the first and second hours, whereas in the whole brain, or various brain areas, maximum MAO-B inhibition (40%) did not occur until 2 h after drug administration. Inhibition in other peripheral organs, such as kidney and small intestine, was of even shorter duration (3 h). After even marked MAO-A inhibition in the liver by moclobemide, the activity recovered within about 4 h when the homogenate was dialysed against water or buffer at 37 degrees C. This rapid recovery is temperature-dependent and does not occur at 18 degrees C. The substance causing the marked inhibition of MAO-A activity when moclobemide is given is probably itself inactivated by the enzyme (reversibility by metabolism). It is expected that more insight into the mechanism of action of moclobemide will be obtained from the use of highly purified preparations of the MAO-A isoenzyme.
Da Prada
M
M
Pharmaceutical Research Department, F. Hoffmann-La Roche, Basle, Switzerland.
Kettler
R
R
Keller
H H
HH
Burkard
W P
WP
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D046508:Culture Techniques; D007527:Isoenzymes / Q000378:metabolism*; D008099:Liver / Q000187:drug effects*; D020912:Moclobemide; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D051381:Rats
D000928:Antidepressive Agents; D001549:Benzamides; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase; D020912:Moclobemide