Clinical pharmacology of moclobemide, a new reversible monoamine oxidase inhibitor

Abstract

The clinical pharmacology of the new reversible monoamine oxidase (MAO) inhibitor, moclobemide, was examined in three separate studies in healthy male volunteers. In a single oral dose study, moclobemide (25-150 mg) was rapidly absorbed from the gastrointestinal tract and had a relatively short plasma half-life (mean 1.3 h after 150 mg). A decrease in the plasma concentrations of the noradrenaline metabolite 4- hydroxy-3-methoxyphenylglycol (HMPG), however, indicated a longer time to peak pharmacodynamic effect and longer duration of activity. Assay of platelet MAO activity did not reveal any evidence of irreversible inhibition of the B form of the isoenzyme. Single oral doses of moclobemide (150 and 300 mg) significantly lowered the threshold to the cardiovascular effects ('cheese reaction') of intravenous tyramine. However, after repeated administration of 100 mg three times daily for over 2 weeks, moclobemide caused significantly less potentiation than did phenelzine (15 mg three times per day) on the cardiovascular effects of oral tyramine, a clinically more relevant model. The MAO-B inhibitor, selegiline (5 mg once daily), also lowered the oral tyramine threshold significantly. Moclobemide was generally well tolerated by these healthy volunteers.

The effects of acute and repeated doses of moclobemide on psychomotor performance and cognitive function in healthy elderly volunteers

“…Moclobemide (p-chloro-N-[2-morpholinoethyl] benzamide) is a novel antidepressant which functions 'by producing a short-lasting reversible inhibition of MAO-A (Da Prada et al, 1981, 1990). Due to its selectivity and reversibility there are significantly fewer problems withmoclobemide in terms of hepatotoxicity and interaction with tyramine (the 'cheese reaction') than with some of the older M A 0 inhibitors (Stab1 et al, 1989;Warrington et al, 1991).…”

“…Moclobemide appears to be relatively free from physical toxicity and has been shown in clinical trials to be well tolerated (Warrington et al, 1991). As the behavioural toxicity of a drug is of great importance in an ageing population, the aim of the present investigation was to evaluate the behavioural effects of this novel MAO-A inhibitor in elderly volunteers.…”

Dietary Tyramine Restriction for Hospitalized Patients on Linezolid

“…Moclobemide, another reversible MAOI drug, has been extensively evaluated in tyramine pressor tests. 11 , 12 As a result, the potential of moclobemide to interact with food has been quantified. The magnitude of the effect observed appears to be similar to that of linezolid.…”