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  • 1
    ISSN: 1432-2072
    Keywords: Clomipramine ; Moclobemide ; Interaction with alcohol ; Psychometric performance ; Body sway ; Anticholinergic effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The interaction of clomipramine and moclobemide with alcohol was compared in a double blind parallel groups study in 24 healthy volunteers. Moclobemide was given at the highest recommended therapeutic dose (200 mg t.i.d.) and clomipramine in a subtherapeutic dose (25 mg b.i.d.) because of its poor tolerance in healthy subjects. Psychometric evaluations were performed during a placebo run-in phase; after a 5-day treatment period; assessments were made before, and again 1 h and 4 h after alcohol ingestion. Alcohol doses were pre-determined for each subject in order to produce a blood alcohol concentration of 0.6 g/l 1 h after alcohol intake and this individual alcohol dose was given on test days. The day before alcohol intake tests for autonomic functions were made to assess the anticholinergic effects of the drugs. Alcohol significantly increased body sway, decreased critical flicker fusion frequency, prolonged choice reaction time, impaired copying skills, impaired memory and increased the subjective feelings of satisfaction and tension. Drugs increased the effect of alcohol on body sway and this was essentially due to clomipramine. Clomipramine both without and with alcohol increased body sway, prolonged choice reaction time more than did moclobemide. Clomipramine seemed to diminish alcohol-induced memory impairment in one of the memory tests used. Subjects taking clomipramine had significantly more adverse effects after alcohol ingestion than did subjects of the moclobemide group. In contrast to moclobemide, clomipramine produced a moderate but significant drop in standing systolic blood pressure and a clear inhibition of salivary excretion. It may be concluded that no important psychometric differences occurred between moclobemide and clomipramine with respect to their interaction with alcohol but moclobemide did not show anticholinergic properties and produced fewer adverse effects than clomipramine in interaction with alcohol.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Key words Monoamine oxidase-A inhibition ; Treatment outcome ; DHPG ; L-dopa ; DOPAC ; HVA ; 5-HIAA ; Moclobemide ; Depressive patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It is generally accepted that the clinical efficacy of monoamine oxidase inhibitors (MAOI) is related to inhibition of this enzyme. In order to evaluate the predictive ability of monoamine oxidase-A inhibition for therapeutic efficacy, the start of treatment effects of moclobemide, a selective, reversible monoamine oxidase-A inhibitor, on plasma concentrations of monoamines and monoamine metabolites were determined. The plasma levels of 3,4-dihydroxyphenylglycol (DHPG, deaminated metabolite of noradrenaline), 5-hydroxyindoleacetic acid (5-HIAA, deaminated metabolite of serotonin), 3,4-dihydroxyphenylacetic acid and homovanillic acid (DOPAC and HVA, deaminated metabolites of dopamine), L-dihydroxyphenylalanine (L-dopa) and noradrenaline were investigated and related to treatment outcome. This was a randomized double blind parallel group study in 47 patients with criteria of major depression according to DSM III R. Moclobemide 300 mg/day, 450 mg/day or 600 mg/day was administered continuously for 6 weeks. Plasma concentrations of monoamine metabolites and monoamines were determined just before treatment by moclobemide, 4 h after the first dose, 24 h after the first dose, before the first dose on day 7, and 4 h after the first dose on day 7. Each moclobemide dose improved depression as measured by MADRS (Montgomery-Asberg Depression Rating scale) but there was no difference between the three doses. Moclobemide dose-dependently reduced plasma concentration of DHPG, L-dopa and HVA. No dose-dependent treatment effect was observed for plasma 5-HIAA, noradrenaline and DOPAC. The clinical outcome as defined by the final MADRS score was not related to any start of treatment changes in plasma monoamine metabolites reflecting inhibition of MAO-A. It is concluded that monoamine oxidase-A inhibition at the beginning of the treatment does not predict clinical outcome.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Moclobemide ; Toloxatone ; Monoamine oxidase-A ; Psychometric performance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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 randomised, 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.
    Type of Medium: Electronic Resource
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