The neurochemical profile of long term oral administration of moclobemide.

Moclobemide, a benzamide derivative, predominantly inhibits the A form of monoamine oxidase (MAO) and its MAO binding is reversible. Acute administration of moclobemide has been shown to induce an increase in brain levels of monoamines and a concomitant decrease in their respective metabolite. In the present study, the drug was administered to rats orally in drinking water at doses of 0.5-1.0 mg/day/rat of an average weight of 250 g for three weeks. This was equivalent to the recommended human dose of 150-300 mg/day. The drug administration did not alter food intake, growth rate and activity of rats. Brain levels of 5-hydroxytryptamine (5-HT) and dopamine (DA) increased. However, increases in 5-hydroxyindoleacetic acid (5-HIAA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) as reported in acute studies were not observed following chronic drug administration in the present study in addition, an increase in brain levels of tryptophan also occurred. Neurochemical profile of long-term moclobemide administration is explainable in terms of an inhibition of MAO activity, increased availability of 5-HT precursor tryptophan and decreased egress of monoamine metabolites.