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  • 1
    Digitale Medien
    Digitale Medien
    Comparative investigation of the effect of moclobemide and toloxatone on monoamine oxidase activity and psychometric performance in healthy subjects (1992)
    Springer
    Psychopharmacology 106 (1992), S. S68 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Moclobemide ; Toloxatone ; Monoamine oxidase-A ; Psychometric performance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02246239
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  • 2
    Digitale Medien
    Digitale Medien
    Initial monoamine oxidase-A inhibition by moclobemide does not predict the therapeutic response in patients with major depression A double blind, randomized study (1996)
    Springer
    Psychopharmacology 127 (1996), S. 370-376 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Key words Monoamine oxidase-A inhibition ; Treatment outcome ; DHPG ; L-dopa ; DOPAC ; HVA ; 5-HIAA ; Moclobemide ; Depressive patients
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002130050100
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  • 3
    Digitale Medien
    Digitale Medien
    Evaluation and comparison of the interaction between alcohol and moclobemide or clomipramine in healthy subjects (1990)
    Springer
    Psychopharmacology 101 (1990), S. 40-45 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Clomipramine ; Moclobemide ; Interaction with alcohol ; Psychometric performance ; Body sway ; Anticholinergic effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02245787
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  • 4
    Digitale Medien
    Digitale Medien
    Expression of a bacterial lysine decarboxylase gene and transport of the protein into chloroplasts of transgenic tobacco (1991)
    Springer
    Plant molecular biology 17 (1991), S. 475-486 
    Details
    ISSN: 1573-5028
    Schlagwort(e): Nicotiana tabacum ; plant transformation ; gene expression ; bacterial lysine decarboxylase ; protein transport ; chloroplasts ; cadaverine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract A possible approach for altering alkaloid biosynthesis in plants is the expression of genes encoding key enzymes of a pathway such as lysine decarboxylase (ldc) in transgenic plants. Two strategies were followed here: one focused on expression of the gene in the cytoplasm, the other on subsequent targeting of the protein to the chloroplasts. Theldcgene fromHafnia alvei was therefore (a) placed under the control of the 1′ promoter of the bidirectional Tr promoter fromAgrobacterium tumefaciens Ti- plasmid, and (b) cloned behind therbcS promoter from potato fused to the coding region of therbcS transit peptide. Bothldc constructs, introduced intoNicotiana tabacum with the aid ofA. tumefaciens, were integrated into the plant genome and transcribed as shown by Southern and northern hybridization. However, LDC activity was only detectable in plants expressing mRNA under the control of therbcS promoter directing the LDC fusion protein into chloroplasts with the aid of the transit peptide domain. In plants expressing the processed bacterial enzyme cadaverine levels increased from nearly zero to 0.3–1% of dry mass.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00040641
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  • 5
    Digitale Medien
    Digitale Medien
    Increased production of cadaverine and anabasine in hairy root cultures of Nicotiana tabacum expressing a bacterial lysine decarboxylase gene (1993)
    Springer
    Plant molecular biology 23 (1993), S. 11-21 
    Details
    ISSN: 1573-5028
    Schlagwort(e): Nicotiana tabacum ; transgenic hairy root cultures ; bacterial lysine decarboxylase ; cadaverine ; anabasine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Several hairy root cultures of Nicotiana tabacum varieties, carrying two direct repeats of a bacterial lysine decarboxylase (ldc) gene controlled by the cauliflower mosaic virus (CaMV) 35S promoter expressed LDC activity up to 1 pkat/mg protein. Such activity was, for example, sufficient to increase cadaverine levels of the best line SR3/1-K1,2 from ca. 50 μg (control cultures) to about 700 μg/g dry mass. Some of the overproduced cadaverine of this line was used for the formation of anabasine, as shown by a 3-fold increase of this alkaloid. In transgenic lines with lower LDC activity the changes of cadaverine and anabasine levels were correspondingly lower and sometimes hardly distinguishable from controls. Feeding of lysine to root cultures, even to those with low LDC activity, greatly enhanced cadaverine and anabasine livels, while the amino acid had no or very little effect on controls and LDC-negative lines.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00021415
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  • 6
    Digitale Medien
    Digitale Medien
    Improved metabolic action of a bacterial lysine decarboxylase gene in tobacco hairy root cultures by its fusion to arbcS transit peptide coding sequence (1996)
    Springer
    Transgenic research 5 (1996), S. 193-201 
    Details
    ISSN: 1573-9368
    Schlagwort(e): Nicotiana tabacum ; transformed root cultures ; metabolic engineering ; lysine decarboxylase ; protein targeting ; Rubisco transit peptide ; anabasine ; cadaverine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The gene of a bacterial lysine decarboxylase (ldc) fused to arbcS transit peptide coding sequence (tp), and under the control of the CaMV 35S promoter, was expressed in hairy root cultures ofNicotiana tabacum. The fusion of theldc to the targeting signal sequence improved the performance of the bacterial gene in the plant cells in many respects. Nearly all transgenic hairy root cultures harbouring the35S-tp-ldc gene contained distinctly higher lysine decarboxylase activity (from 1.5 to 30 pkat LDC per mg protein) than those which had been transformed with constructs in which the gene had been directly cloned behind the CaMV 35S promoter. The higher enzyme activity led to the accumulation of up to 0.7% cadaverine on a dry mass basis. In addition, part of the cadaverine pool was used for increased biosynthesis of anabasine, an alkaloid which was hardly detectable in control cultures. The best line contained anabasine levels of 0.5% dry mass, which could further be enhanced by feeding of lysine.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01969709
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