Comparative investigation of the effect of moclobemide and toloxatone on monoamine oxidase activity and psychometric performance in healthy subjects.
The effects of moclobemide and toloxatone, two reversible monoamine oxidase-A inhibitors, on biochemical parameters that reflect monoamine metabolism and on psychomotor performance parameters were investigated in a study in 12 healthy volunteers. Treatments were given double-blind in a randomized, placebo-controlled cross-over design, with 1 week wash-out between the treatments. Drugs were given thrice daily in the following doses: moclobemide 150-150-150 mg and toloxatone 400-200-400 mg. All assessments were performed on day 8 under standardized conditions. There was no difference with regard to adverse events between moclobemide and toloxatone: both drugs induced a slight decrease in both supine and standing heart rate. Judged on the basis of the area under the curve, the two MAO-inhibitors reduced the plasma levels of DHPG and HVA, with more pronounced effects for moclobemide than for toloxatone. After moclobemide MAO-A inhibition was almost constant over 24 h, whereas the effect of toloxatone was short lasting after each dose. The same differences were reflected in plasma 5-HIAA concentrations and urinary excretion of 3-methoxytyramine and normetanephine. Neither of the compounds tested had any influence on the memory, vigilance, mood, or sleeping habits of the subjects.
Dingemanse
J
J
Department of Clinical Pharmacology, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Berlin
I
I
Payan
C
C
Thiede
H M
HM
Puech
A J
AJ
D000328:Adult; D001143:Arousal / Q000187:drug effects; D001549:Benzamides / Q000009:adverse effects / Q000494:pharmacology*; D015306:Biogenic Monoamines / Q000097:blood / Q000652:urine; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects; D020912:Moclobemide; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D010080:Oxazoles / Q000009:adverse effects / Q000494:pharmacology*; D023303:Oxazolidinones; D011597:Psychomotor Performance / Q000187:drug effects*; D012890:Sleep / Q000187:drug effects
D001549:Benzamides; D015306:Biogenic Monoamines; D008996:Monoamine Oxidase Inhibitors; D010080:Oxazoles; D023303:Oxazolidinones; C010798:toloxatone; D008995:Monoamine Oxidase; D020912:Moclobemide