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.
1. The effects of two reversible, predominantly monoamine oxidase-A (MAO-A) inhibitors, moclobemide (150 mg three times daily) and toloxatone (400-200-400 mg day-1) on monoamine metabolites and psychometric performance were compared in a double-blind placebo controlled crossover study in 12 healthy subjects. 2. After 7 days of moclobemide/toloxatone/placebo administration subjects were hospitalized for 24 h on day 8. Blood samples were drawn every 2 h for determination of plasma noradrenaline (NA), 3,4-dihydroxyphenylglycol (DHPG), homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA). Urine was collected for measurements of normetanephrine and 3-methoxytyramine excretion. Psychometric performance (short- and long-term memory, critical flicker fusion frequency, choice reaction time) and subjective feelings were assessed before each drug intake (in the morning, at noon, in the evening). 3. Compared with placebo, both reversible monoamine oxidase inhibitors decreased the plasma concentration of DHPG and HVA. The overall fall in DHPG (AUC from 0 to 24 h) was 44% during moclobemide and 12% during toloxatone (P less than 0.001) and the overall decrease in HVA was 38% and 20% (P less than 0.005) on moclobemide and toloxatone, respectively. 4. Before the next drug intake, MAO-A inhibition, as judged by the decrease of plasma DHPG concentration, was significantly different from placebo with moclobemide but not with toloxatone. 5. Moclobemide, but not toloxatone, exerted a moderate, but significant inhibition of the deamination of 5-hydroxytryptamine (5-HT) as judged by the fall in plasma 5-HIAA concentration. Neither drug influenced plasma NA concentration. 6. A significant rise in urinary excretion of normetanephrine was observed on moclobemide and to a lesser extent on toloxatone. The urinary excretion of 3-methoxytyramine was significantly raised by moclobemide but not by toloxatone. 7. Neither moclobemide nor toloxatone altered memory function, vigilance, subjective feelings or sleep characteristics of the subjects.
Berlin
I
I
Department of Clinical Pharmacology, Hôpital Pitié-Salpêtrière, Paris, France.
Zimmer
R
R
Thiede
H M
HM
Payan
C
C
Hergueta
T
T
Robin
L
L
Puech
A J
AJ
D000328:Adult; D001549:Benzamides / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D004311:Double-Blind Method; D006719:Homovanillic Acid / Q000097:blood; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000097:blood; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000097:blood; D020912:Moclobemide; D008996:Monoamine Oxidase Inhibitors / Q000097:blood / Q000494:pharmacology*; D010080:Oxazoles / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D023303:Oxazolidinones; D011594:Psychometrics; D011603:Psychophysiology
D001549:Benzamides; D008996:Monoamine Oxidase Inhibitors; D010080:Oxazoles; D023303:Oxazolidinones; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; C010798:toloxatone; D020912:Moclobemide; C010117:3,4-dihydroxyphenylglycol; D006719:Homovanillic Acid