Inhibition of monoamine oxidase by moclobemide: effects on monoamine metabolism and secretion of anterior pituitary hormones and cortisol in healthy volunteers.

Abstract

1. Single oral doses (100, 200 and 300 mg) of moclobemide, a reversible inhibitor of monoamine oxidase (MAO) with predominant effects on the A‐ type of the enzyme, were administered to eight young, healthy male volunteers in a double‐blind, random‐order, placebo‐controlled study. The investigation was thereafter continued in an open fashion by administering a single 10 mg dose of the MAO‐B inhibitor deprenyl to the same subjects. 2. Deamination of catecholamines was powerfully and dose‐dependently inhibited by moclobemide, as evidenced by up to 40% decreases in the urinary excretion of deaminated catecholamine metabolites, corresponding increases in the excretion of non‐ deaminated, methylated metabolites, and up to 79% average decreases in the plasma concentration of 3,4‐dihydroxyphenylglycol (DHPG), a deaminated metabolite of noradrenaline (NA), and up to 75% average decreases in the plasma concentrations of 3,4‐dihydroxyphenylacetic acid (DOPAC), a deaminated metabolite of dopamine. The urinary excretion of 5‐hydroxyindoleacetic acid (5‐HIAA) was only slightly reduced. In contrast, deprenyl, in a dose which almost totally inhibited MAO‐B activity in blood platelets, did not appreciably affect the plasma concentrations of DHPG or DOPAC. 3. Due to the rapid, reversible, dose‐dependent and MAO‐A specific effect of moclobemide on plasma concentrations of DHPG, it is suggested that DHPG in plasma may be a useful indicator of the magnitude and duration of MAO‐A inhibition in man. 4. Sympatho‐adrenal function at rest was not significantly altered by moclobemide, as judged by unchanged plasma catecholamine concentrations and stable blood pressure and heart rate recordings. 5. Monoamine oxidase type B activity in blood platelets was slightly (less than 30%) and transiently inhibited after moclobemide. 6. The secretion of prolactin was dose‐dependently stimulated by moclobemide, whereas the plasma concentrations of growth hormone (hGH) and cortisol remained unchanged.

Comparison of the monoamine oxidase inhibiting properties of two reversible and selective monoamine oxidase‐A inhibitors moclobemide and toloxatone, and assessment of their effect on psychometric performance in healthy subjects.

“…This may be the result of dietary non-compliance. However, the effect of moclobemide on the deamination of 5-HT is known to be moderate (Koulu et al, 1989) probably because the affinity of the drug to the binding sites of the MAO is less than that of serotonin.…”

“…Moclobemide is a new, reversible (Waldmeier, 1985) MAO-A selective (Koulu et al, 1989;Wiesel et al, 1985) MAOI with few adverse effects and clear antidepressant properties (Casacchia et al, 1984;Dajas et al, 1984;Larsen et al, 1984;Stabl et al, 1989). Moclobemide penetrates well the brain, maximal concentrations of moclobemide in CSF are reached 2 h after oral administration and high CSF/plasma ratio (0.5) can be obtained (Lauy et al, 1990).…”

Human Pharmacology of Ayahuasca: Subjective and Cardiovascular Effects, Monoamine Metabolite Excretion, and Pharmacokinetics

“…The low plasma levels found for harmine in the present study could explain the absence of a clear-cut MAO inhibitor effect on the urinary excretion of monoamine metabolites. The acute administration of a MAO-A inhibitor induces a decrease in the levels of oxidized deaminated monoamine metabolites and an increase in the levels of COMT-dependent methylated compounds (Pletscher, 1966;Koulu et al, 1989). Whereas in the present study normetanephrine, a methylated breakdown product of norepinephrine, showed statistically significant increases after dosing with ayahuasca, the levels of the deaminated metabolites measured, i.e., VMA, HVA, and 5-HIAA, did not show decreases but, rather, were nonsignificantly increased.…”

“…In vivo and in vitro studies have shown that when MAO is pharmacologically inhibited, the levels of MAO-dependent deaminated metabolites decrease and those of COMT-dependent methylated metabolites increase. In humans, MAO inhibitors decrease, after acute administration, the urinary excretion of vanillylmandelic acid (VMA), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA), the deaminated metabolites of norepinephrine/epinephrine, dopamine, and serotonin, respectively, while increasing that of metanephrine and normetanephrine, the methylated metabolites of epinephrine and norepinephrine, respectively (Pletscher, 1966;Koulu et al, 1989). Monoamine metabolites have both a CNS and a non-CNS origin, and their assessment in urine does not give information regarding the organ in which MAO was inhibited.…”

MAO‐B Inhibition by a Single Dose of l‐Deprenyl or Lazabemide Does Not Prevent Neuronal Damage Following Focal Cerebral Ischaemia in Rats

“…The brain homogenate was stored at ª80ae until use. The MAO-A activity was determined according to Borbe et al (1990) and the MAO-B activity was determined according to Koulu et al (1989). The results were calculated as picomoles deaminated metabolite (5-hydroxyindole acetic acid or phenyl acetic acid) formed per min.…”