Biochemical effects of high single doses of moclobemide in man: correlation with plasma concentrations

Abstract

The effects of high single doses of moclobemide (300, 450 and 600 mg given at the end of a standardized meal) on plasma levels of several catecholamines and their deaminated metabolites, and on plasma levels of pituitary hormones were determined in eight healthy young male volunteers in a randomized, double-blind, placebo-controlled study. Assessment of the i.v. tyramine potentiation and determination of the plasma levels of moclobemide were also performed. The tyramine sensitivity factor at 2 h after dosing was about 2.1, with no significant differences between the doses used. The inhibitory activity of moclobemide on MAO-A was reflected in significant reductions of plasma concentrations of DHPG and 5-HIAA. No clear differences were detected between the moclobemide doses. Prolactin plasma concentrations were only slightly increased after the two higher doses. The plasma concentrations of moclobemide were very much in agreement with those found in previous studies under similar experimental conditions. Thus, single oral doses of 300, 450 and 600 mg moclobemide demonstrated marked inhibition of MAO-A activity, whereas a single dose of 300 mg induced a near-maximum effect.

Effect of oral linezolid on the pressor response to intravenous tyramine

“…times greater with placebo than with moclobemide. The result confirms a statistically significant difference between the TYR30 of moclobemide and placebo, and is in keeping with previous literature citations [3,14]. The TSF for linezolid was calculated to be 1.8 (90% CI 1.6, 2.0, P < 0.0001), so the dose of tyramine required to cause a 30-mmHg rise in SBP was 1.8 times greater with placebo than with linezolid.…”

The effects of moclobemide on the pharmacokinetics of the 5‐HT1B/1D agonist rizatriptan in healthy volunteers

“…Inhibition of MAO‐A by moclobemide is directly related to its plasma concentration. Maximum effects, as measured by decreases in plasma concentrations of DHPG (3,4‐dihydroxphenylglycol, a circulatory metabolite of noradrenaline), are apparent at moclobemide plasma levels greater than 1000 ng ml −1 [9]. Although monoamine oxidase inhibitors are currently infrequently used for depression, it is possible that some migraineurs could be taking MAO inhibitors chronically.…”

Monoamine oxidase‐A: pharmacodynamics in humans of moclobemide, a reversible and selective inhibitor.

“…moclobemide, DHPG and Dose-dependence in several parameters was found. ia after a single dose of 300 mg A decrease in clearance and increase in bioavailubject6).…”

“…However, an indirect measure of MAO-A activity is provided by the plasma concentrations of monoamine metabolites which are formed by MAO-A. The time courses of two metabolites, 3,4-dihydroxyphenylglycol (DHPG) and 5-hydroxyindoleacetic acid (5HIAA), following single oral doses of moclobemide have been studied previously [5,6]. We have used the results published by the latter group to conCorrespondence: Professor Dr T. W. Guentert, Department of Basel, Switzerland struct a physiological pharmacokinetic-pharmacodynamic model to describe MAO-A inhibition.…”