Inhibition of monoamine oxidase by moclobemide: effects on monoamine metabolism and secretion of anterior pituitary hormones and cortisol in healthy volunteers.
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.
Koulu
M
M
Department of Pharmacology, University of Turku, Finland.
Scheinin
M
M
Kaarttinen
A
A
Kallio
J
J
Pyykkö
K
K
Vuorinen
J
J
Zimmer
R H
RH
D015102:3,4-Dihydroxyphenylacetic Acid / Q000097:blood; D000328:Adult; D001549:Benzamides / Q000494:pharmacology*; D001792:Blood Platelets / Q000201:enzymology; D002395:Catecholamines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004837:Epinephrine / Q000097:blood; D006719:Homovanillic Acid / Q000652:urine; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D006897:Hydroxyindoleacetic Acid / Q000652:urine; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000097:blood; D020912:Moclobemide; D008995:Monoamine Oxidase / Q000097:blood; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood; D010908:Pituitary Hormones, Anterior / Q000378:metabolism*; D011897:Random Allocation; D012642:Selegiline / Q000494:pharmacology; D014642:Vanilmandelic Acid / Q000652:urine
D001549:Benzamides; D002395:Catecholamines; D008996:Monoamine Oxidase Inhibitors; D010908:Pituitary Hormones, Anterior; D015102:3,4-Dihydroxyphenylacetic Acid; D012642:Selegiline; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D014642:Vanilmandelic Acid; D008995:Monoamine Oxidase; D020912:Moclobemide; C010117:3,4-dihydroxyphenylglycol; D006854:Hydrocortisone; D009638:Norepinephrine; D006719:Homovanillic Acid; D004837:Epinephrine