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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 55 (1982), S. 1-8 
    ISSN: 1435-1463
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The dibutyryl analogues of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were administered into the lateral ventricles and catecholamine metabolites were determined in brain 40 min later. Dibutyryl cAMP elevated the level of homovanillic acid in whole brain and dihydroxyphenyl acetic acid levels in striatum, the dopamine-rich part of the limbic system and hemispheres but neither affected the accumulation of 3-methoxytyramine following inhibition of MAO with pargyline nor dopamine and noradrenaline levels. Normetanephrine accumulating after MAO inhibition was elevated markedly by dibutyryl cAMP. Dibutyryl cGMP was without effect on the catecholamine metabolites investigated. Dibutyryl cAMP appears to stimulate dopamine metabolism within dopaminergic nerve endings but does not stimulate dopamine release. Dibutyryl cAMP-induced activation of noradrenaline metabolism, however, appears to coincide with a stimulation of noradrenaline release.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 318 (1981), S. 19-28 
    ISSN: 1432-1912
    Keywords: 3,4-Dihydroxyphenylacetic acid ; 3,4-Dihydroxymandelic acid ; 3,4-Dihydroxyphenylethanol ; 3,4-Dihydroxyphenylglycol ; Radioenzymatic determination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An assay is described for the simultaneous determination of dopamine, noradrenaline, adrenaline, dopa, 3,4-dihydroxyphenylacetic acid, 3,4-dihydroxyphenyl-ethanol, 3,4-dihydroxymandelic acid and 3,4-dihydroxy-phenylglycol, capable of detecting amounts in the femtomol range. The assay is based on the O-methylation of the catechol moiety utilizing S-[3H-methyl]-adenosyl-l-methionine and a partially purified catechol-O-methyl transferase to form the various O-[3H-methyl]-catechol derivatives. The O-[3H-methyl]-catechol derivatives are purified by thin layer chromatography, solvent partitions and/or ion exchange chromatography. The assay was successfully applied to biological sample. It was possible for the first time, to detect free 3,4-dihydroxy-phenylglycol, free 3,4-dihydroxyphenylethanol and 3,4-dihydroxymandelic acid in a small volume (25μl) of blood plasma of man, rat, dog and rabbit. The conjoint measurement of catecholamines and their catechol metabolites in minute amounts of biological samples may contribute to a more detailed understanding of catecholamine metabolism in the peripheral and central nervous system.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 318 (1981), S. 29-35 
    ISSN: 1432-1912
    Keywords: Catecholamine metabolism ; Rat brain ; MAO inhibitors ; Reserpine ; l-Dopa
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The neutral and acidic catechol metabolites of noradrenaline and dopamine in rat brain were determined with a newly developed radioenzymatic method utilizing O-3H-methylation of the catechol moiety by catechol-O-methytransferase (COMT) and S-[3H-methyl]-adenosyl-l-methionine. 1. In the brain of rats killed by microwave irradiation the distribution of dihydroxyphenylethanol (DOPET) and dihydroxyphenylacetic acid (DOPAC) was uneven and similar to the distribution of dopamine. Dihydroxyphenylglycol (DOPEG) levels were highest in the noradrenaline-rich brain regions. In contrast, dihydroxymandelic acid (DOMA) was almost evenly distributed. 2. Following decapitation the concentration of the neutral metabolites DOPET and DOPEG was 2.5 to 8-fold higher. DOMA levels did not differ from those of microwave-irradiated brain tissue. 3. When administered i.p. 60 min before sacrifice the monoamine oxidase (MAO) inhibitors pargyline, nialamide or tranylcypromine markedly reduced the concentration of DOPET, DOPAC and DOPEG but did not affect the level of DOMA. 4. Administration of l-dopa together with benserazide led to a pronounced increase of DOPET and DOPAC in rat striatum. Inhibition of COMT by tropolone augmented the l-dopa-induced increase of DOPET and DOPAC. 5. Reserpine, 10 mg/kg i.p., caused an immediate increase (within 15 min) of DOPAC levels in the dopamine-rich brain part which lasted up to 60 min. Despite an increased dopamine catabolism via MAO, DOPET levels were not increased but rather decreased at 1 and 3h. Reserpine induced an initial and transient increase of DOPEG levels which was enhanced by simultaneous administration of tropolone. The level of DOMA was not changed by reserpine. The data suggest that metabolism of endogenous dopamine to DOPET constitutes a minor pathway. With regard to catechol metabolites, dopamine appears to be metabolized mainly to DOPAC. The main, if not exclusive catechol metabolite of noradrenaline appears to be DOPEG. Rapid diffusion and further metabolism are probably responsible for the low steady-state level of DOPEG. In rat brain the catabolism of endogenous noradrenaline to DOMA appears to represent a very minor pathway.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 316 (1981), S. 299-303 
    ISSN: 1432-1912
    Keywords: Endogenous dopa ; Rat brain ; Microwave irradiation ; Radioenzymatic determination ; α-Methyl-p-tyrosine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary dopa was isolated from rat brain by cation exchange chromatography and determined by a radioenzymatic method using catechol-O-methyl-transferase and [3H]-S-adenosyl-methionine as cofactor. The product [3H]-methoxytyrosine was purified by cation and anion exchange chromatography. For identification of presumed endogenous dopa isolated from rat brain and rat blood plasma the [3H]-labelled product was purified further by thin-layer chromatography. In the brain of rats killed by decapitation, dopa in a concentration of 7 ng/g was identified. When unstressed rats were killed by focussed microwave irradiation at 2.450 MHz and 8 kW for 1.3 s dopa levels as high as 20 ng/g were measured. The regional distribution of dopa in brain of rats killed by microwaves was similar to the distribution of catecholamines, dopa levels being highest in c. striatum and lowest in cerebellum. Inhibition of tyrosine hydroxylase with α-methyl-p-tyrosine methylester HCl, 250 mg/kg i.p. 90 min before death did not change the brain dopa levels in rats killed by decapitation or in rats killed by microwaves. Compounds, such as haloperidol, chlorpromazine, apomorphine and pentobarbital which are known to increase or decrease catecholamine synthesis did not change the basal level of dopa. The data indicate that in rat brain, the main portion of dopa is associated with catecholamine-containing nerve terminals and that this portion is present in a pool which is only slowly metabolized. A second very small pool of dopa must exist, which is serving as precursor pool for catecholamines and which is turned over at a higher rate. It can be concluded that the basal dopa level cannot be used as an indicator of catecholamine synthesis.
    Type of Medium: Electronic Resource
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  • 5
    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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