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  • 1
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Journal of medicinal chemistry 19 (1976), S. 725-727 
    ISSN: 1520-4804
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 262 (1976), S. 596-598 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The patients studied were newly hospitalised with a diagnosis of depression. None of them had used tricyclic antidepressants or any other drugs known to interfere with the amine transport mechanisms for at least two days before the study commenced and some of them had never used antidepressants. ...
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: depression ; Serotonin ; Blood platelets ; Imipramine ; Amoxapine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 5-Hydroxytryptamine (5-HT) uptake was studied by using blood platelets from 13 patients with endogenous depression (Hamilton rating scale 33±7) and 13 healthy volunteers. An improved method with a short incubation time and low substrate concentration was used, and the incubation was performed in Krebs-Henscleit buffer (pH 7.4) at 37° C. A clear difference in 5-HT uptake by blood platelets was noted: The V max of the reaction in patients was 39, and in controls 71 pmol per 2×107 platelets in 5 min. There was no significant difference in the K m. After a 4-week treatment with imipramine, a competitive inhibition of 5-HT uptake with an increased K m was seen; after a similar treatment with amoxapine there was little change in 5-HT uptake. Amoxapine was inferior to imipramine as an inhibitor of 5-HT uptake, also in vitro. There was no difference in clinical recovery in these treatment groups. These results may be of importance so as to understand the potential biological differences between depressed patients and normal persons.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 279 (1973), S. 371-380 
    ISSN: 1432-1912
    Keywords: Serotonin ; Dopamine ; Noradrenaline ; Alkaloids ; Synaptosomes ; Brain Chemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of some tetrahydroharmane derivatives on the synaptosomal uptake of monoamines was studied. 1,2,3,4-Tetrahydroharmane (TH), which can be viewed as an analog of tryptamine, inhibited 5-hydroxytryptamine (5-HT), noradrenaline (NA) and dopamine (DA) uptake, but TH was about 10 times less potent than tryptamine. 6-Hydroxy-1,2,3,4-tetrahydroharmane (6-HTH), a 5-HT analog, was slightly more potent an inhibitor of 5-HT uptake than TH, but as catecholamine uptake inhibitors these compounds were equipotent. Harmane-1,2,3,4-tetrahydro-3-carboxylic acid had no effect. Salsolinol and salsolidine, tetrahydroisoquinoline derivatives, were less potent than the harmane derivatives. It is to be concluded that also tetrahydroharmane derivatives have an affinity to the amine “pump” similarly to that of the tetrahydroisoquinolines, which are the corresponding analogs of catecholamines. These kinds of compounds are important because of the possibility that they may be formed in physiological conditions as condensation products of biogenic amines and aldehydes, e.g. acetaldehyde, which is an intermediate of ethanol metabolism.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2072
    Keywords: Serotonin ; Noradrenaline ; Amitriptyline ; Nortriptyline ; Blood platelets ; Synaptosomes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To estimate the inhibition of amine uptake caused in vivo by tricyclic drugs used at a clinical dose, normal human blood platelets or rat hypothalamic or cortical synaptosomes were incubated with 3H-5-hydroxytryptamine (3H-5-HT) or 3H-noradrenaline (3H-NA) in platelet-free plasma of healthy volunteers receiving a single dose of 50 mg amitriptyline (AT) or nortriptyline (NT) orally. Venous blood samples were taken 2–72 h after drug administration. AT and NT were assayed gas-chromatographically. The uptake-inhibiting potency in the plasma samples was measured as a percentage of the uptake in control plasma taken before drug administration. The observed effect was compared with the uptake inhibition caused by known concentrations of the drug added to control plasma in vitro. In most experiments there was a correlation between the gas-chromatographically assayed AT or NT and uptake inhibition. 5-HT uptake in platelets was inhibited by both drugs, and so was NA uptake in rat cortical synaptosomes. 5-HT uptake by hypothalamic synaptosomes, however, was not sensitive enough to reveal the small concentrations of drugs. In platelets a poor correlation was found 12 h post AT administration, since the effect found in the biological assay outlasted the chemically assayed AT and NT. Tricyclic antidepressants are metabolized to a variable degree to both active and inactive metabolites. After AT, its active demethylated metabolite NT did not seem to explain the effect; recently potent 2-hydroxylated metabolites of imipramine have been postulated. It remains to be clarified whether or not such active (as yet unidentified) metabolites of AT and NT contribute to their uptake-inhibiting effects. Neither drug showed any remarkable specificity as to NA or 5-HT uptake.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 21 (1971), S. 202-211 
    ISSN: 1432-2072
    Keywords: Diazepam ; Diphenhydramine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The immediate effects on the mood and some mental and physical functions of a single oral dose of diazepam (10 mg) and diphenhydramine (50 mg) compared with placebo were studied in healthy human subjects. The material comprised 270 students divided into three similar groups. The mood was tested by the Nowlis adjective check list. The digit symbol test and number series were used to test the mental condition. The major significant results of the study were: diazepam decreased activity both in men and women and sociability in women. It increased euphoria in men and depressivity and withdrawing in women. It impaired the results in the digit symbol test and the ability to repeat the number series in both men and women. Diphenhydramine also decreased activity in men and women. It caused some euphoria in men. It had a slighter depressing effect than diazepam on the mental functions. The many different effects in women as compared with men did not seem to be caused only by larger dose per kg given to the former. This was confirmed by an additional study in which a smaller group of men was given the same dose/kg of the drugs as the women in the main study, and vice versa.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0738
    Keywords: Key words 2 ; 3 ; 7 ; 8-Tetrachlorodibenzo-p-dioxin ; TCDD ; Phosphoenolpyruvate carboxykinase ; PEPCK ; Glucose ; Glycogen ; Amino acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Reduced gluconeogenesis due to decreased activity of key gluconeogenic enzymes in liver, together with feed refusal, has been suggested to play an important role in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced lethality in rats. This study was carried out to further analyse the toxicological significance of reduced gluconeogenesis by comparing dose-responses and time-courses of effects of TCDD on the activity of phosphoenolpyruvate carboxykinase (PEPCK) in liver, liver glycogen concentration as well as plasma concentrations of glucose and amino acids in both genders of TCDD-sensitive Long-Evans (L-E) rats and TCDD-resistant Han/Wistar (H/W) rats. A dose-dependent decrease in PEPCK activity was observed in H/W rats, but in L-E rats the activity was not decreased. However, TCDD impaired the strong increase in liver PEPCK activity observed in pair-fed controls of the L-E strain. Liver glycogen concentrations were severely decreased in L-E rats and moderately in H/W rats. This effect seems to be secondary to reduced feed intake, since a similar decrease was seen in pair-fed controls. Decreases in plasma glucose concentrations were also more profound in L-E rats than in H/W rats, but pair-fed controls were generally less affected. Circulating concentrations of amino acids were markedly increased in TCDD-treated L-E rats, which is likely to reflect increased mobilization of amino acids and their decreased metabolism in liver. Reduction of liver PEPCK activity cannot account for the sensitivity difference of these two strains of rats in terms of mortality. Nevertheless, the response of both strains of TCDD-treated rats regarding gluconeogenesis is different from that seen in pair-fed controls and suggesting that impairment of this pathway contributes to the development of the wasting syndrome.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 57 (1985), S. 268-271 
    ISSN: 1432-0738
    Keywords: Methyl mercury ; Dopamine uptake ; Dopamine receptors ; Serotonin uptake ; Benzodiazepine receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Methyl mercury inhibits dopamine (DA) and serotonin (5-HT) uptake by brain synaptosomes and decreases antagonist binding to striatal dopaminergic D2 receptors in vitro. To assess the effects in vivo, adult rats were given methyl mercury, either as a single dose (10 mg/kg by gavage) or a cumulative total dose of 50 mg/kg in 2 weeks. The repeated dosing decreased body weight and caused neuromuscular dysfunction. In spite of this overt toxicity, neither 3H-DA uptake nor 3H-haloperidol binding changed in striatal synaptosomes. There were no significant alterations in 3H-5-HT uptake by hypothalamic synaptosomes or 3H-flunitrazepam binding in cerebellar synaptosomes. The results suggest that monoaminergic synapses and the benzodiazepine binding sites, associated with cerebellar GABA receptors, remain functionally normal at doses of methyl mercury that are otherwise toxic. The results also emphasize the importance of due care when extrapolating cellular or biochemical data to the level of the whole organism.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0738
    Keywords: Key words 2 ; 3 ; 7 ; 8-Tetrachlorodibenzo-p-dioxin ; Species differences ; Acute toxicity ; Serotonin ; Tryptophan ; Gluconeogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We have previously reported that in rats 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) lethality is associated (although not necessarily causally) with changes in brain serotonin (5-HT) metabolism. In the present study, we have examined whether this holds for other species by comparing the effect of TCDD in the most TCDD-susceptible and the most TCDD-resistant species, guinea pigs and hamsters, respectively. Body weight gain of guinea pigs exposed to TCDD (0.3–2.7 μg/kg) diminished dose dependently, while the effect was marginal in hamsters (900–4600 μg/kg). Brain 5-hydroxyindoleacetic acid (the main metabolite of brain 5-HT), brain tryptophan (the precursor amino acid of 5-HT), and plasma free and total tryptophan were not affected at any dose in guinea pigs. In contrast, 4 days after exposure, the levels of plasma free and total tryptophan were consistently increased in hamsters. These, as well as brain tryptophan, were still elevated 10 days after exposure. TCDD did not affect plasma glucose level in either species. Liver glycogen was decreased in a dose-dependent manner in TCDD-treated guinea pigs as well as in their pair-fed controls on day 10. There was no change in liver glycogen in hamsters. The activity of the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase was only depressed in hamsters by all doses of TCDD. We conclude that changes in tryptophan metabolism or in carbohydrate homeostasis cannot explain the wide interspecies differences in susceptibility to the acute lethality of TCDD, although they may correlate with some aspects of its toxicity in certain species.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0738
    Keywords: Key words 2 ; 3 ; 7 ; 8-Tetrachlorodibenzo-p-dioxin ; TCDD ; 1 ; 2 ; 3 ; 7 ; 8-Pentachlorodibenzo-p-dioxin ; 1 ; 2 ; 3 ; 4 ; 7 ; 8-Hexachlorodibenzo-p-dioxin ; 1 ; 2 ; 3 ; 4 ; 6 ; 7 ; 8-Heptachlorodibenzo-p-dioxin ; Tryptophan metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We compared the effects of 2,3,7,8-tetra (TCDD), 1,2,3,7,8-penta (PeCDD), 1,2,3,4,7,8-hexa (HxCDD) and 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD) on brain serotonin metabolism, plasma tryptophan and liver tryptophan pyrrolase activity in two rat strains, TCDD-sensitive Long-Evans (Turku AB; L-E) and TCDD-resistant Han/Wistar (Kuopio; H/W). Previously it was shown that L-E rats exhibit the expected rank order of potency for CDDs in terms of acute toxicity with TCDD being the most potent, followed by PeCDD, HxCDD and HpCDD. In contrast, to H/W rats HxCDD was the most toxic and TCDD the least toxic of these congeners. In the present study, the CDDs decreased body weight in L-E rats in the following order of potency: TCDD〉PeCDD〉HxCDD〉HpCDD. The same rank order was recorded for elevations in brain tryptophan and plasma free tryptophan concentrations as well as for inhibition of the main hepatic tryptophan metabolizing enzyme, tryptophan pyrrolase. By contrast, in H/W rats HxCDD was the most effective congener in producing loss of body weight, followed by HpCDD, PeCDD and TCDD. This was also true of changes in tryptophan homeostasis. These findings imply that in TCDD-susceptible L-E and TCDD-resistant H/W rats the potency of dioxin congeners in inducing acute toxicity highly correlates with their ability to disrupt tryptophan homeostasis. However, there may not be a direct causal relationship between body weight loss and altered tryptophan homeostasis, because the magnitudes of these two phenomena were not consistently parallel across the dioxin congeners tested.
    Type of Medium: Electronic Resource
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