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  • 1
    Electronic Resource
    Electronic Resource
    Nocturnal plasma levels of cytokines in healthy men (1992)
    Springer
    European archives of psychiatry and clinical neuroscience 242 (1992), S. 53-56 
    Details
    ISSN: 1433-8491
    Keywords: Cytokines ; Interleukin-1β ; Interleukin-6 ; Tumor-necrosis-factor ; Sleep
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Nocturnal cytokine levels were measured serially in 12 healthy male volunteers for 12 h, including 8 h of polygraphically monitored nocturnal sleep. Plasma concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were determined in 30-min intervals by enzyme-linked immunoadsorbant assays. In some subjects cytokines were not detectable at all. In the remaining volunteers (27% for IL-1β, 58% for IL-6 and TNF-α, respectively) occasional values near to the detection limits (DL) of the assays could be measured. With respect to IL-1β and IL-6, plasma levels above the DL were significantly more frequent during sleep than during the preceding time of wakefulness. No temporal association with NREM or REM episodes could be shown. TNF-α values above the DL were randomly distributed across the 12-h period investigated. It is concluded that in a considerable percentage of healthy subjects small amounts of cytokines are released at night. Release of IL-1β and IL-6 is temporally associated with sleep, whereas the release of TNF-α is not. It remains to be established whether nocturnal cytokine release reflects either an interaction between sleep and host defense mechanisms or a sleep-independent circadian rhythmicity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02190343
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  • 2
    Electronic Resource
    Electronic Resource
    Antiglucocorticoid treatment disrupts endocrine cycle and nocturnal sleep pattern (1992)
    Springer
    European archives of psychiatry and clinical neuroscience 241 (1992), S. 372-375 
    Details
    ISSN: 1433-8491
    Keywords: Mifepriston ; RU 486 ; Cortisol ; ACTH ; sleep ; antiglucocorticoids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Mifepriston (RU 486) is a steroid antagonist which binds with high affinity to glucocorticoid receptors (GR), and also to progesterone receptors. The antiglucocorticoid action of Mifepriston in man has been demonstrated by blockade of the negative feedback action of endogenous cortisol and by antagonism of the effects of exogenously aministered dexamethasone. In the present study Mifepriston was administered to a normal male volunteer at 14.00 h and its effects on pituitary-adrenal activity and nocturnal sleep pattern were recorded. Mifepriston caused a large rise in plasma ACTH levels during the morning hours in comparison to untreated male control subjects. Plasma ACTH levels in the Mifepriston treated subject at 7.00 h were threefold greater than in the control subjects (104.4 pg/ml vs. 37.6±13.9 pg/ml; $$\bar x$$ ±SD). Subsequently the cortisol secretion was enhanced and the rise was advanced by about 60 minutes compared to controls. The main effects of Mifepriston on EEG sleep pattern were a dramatic disruption of sleep quality with a prolonged sleep onset latency, increased nocturnal awakenings and a considerable reduction of both slow wave sleep (SWS) and REM sleep. After Mifepriston, SWS was reduced by about 80% in comparison to placebo, and REM sleep was reduced by more than 50%. While the present data were collected from only a single subject the effects observed were so pronounced that tentative conclusions seem to be justified: The well-established pharmacological properties of Mifepriston as a glucocorticoid antagonist are reflected by its action on sleep physiology since it influences sleep in a direction opposite to that produced by cortisol. This observation further substantiates the view that changes in SWS and REM sleep may be mediated by GR effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02191963
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Open clinical trial on the sigma ligand panamesine in patients with schizophrenia (1997)
    Springer
    Psychopharmacology 132 (1997), S. 82-88 
    Details
    ISSN: 1432-2072
    Keywords: Key words Panamesine ; Sigma ligand ; Schizophrenia ; Atypical antipsychotic drug ; Extrapyramidal symptoms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The sigma (σ) receptor has been proposed as a target of neuroleptic drugs. Preclinical data suggest that panamesine (EMD 57445), a novel σ ligand, has antipsychotic effects and is free of side effects related to the extrapyramidal motoric system (EPMS). Here we report the results of an exploratory study aimed at determining the appropriate dose range and the safety of panamesine in patients with an acute episode of schizophrenia. The first trial with four patients revealed insufficient clinical efficacy of a protocol where the daily dosage was increased stepwise from 7.5 mg during week 1, up to 30 mg during weeks 3 and 4. In a second set of trials, 12 patients received 15 mg at the beginning, this being increased up to 60 mg/day within 3 days and then maintained at this level for 4 weeks. As assessed by a decrease in the Brief Psychiatric Rating Scale score by at least 50%, five patients were judged as responders, whereas six patients showed only a slight improvement, and one deteriorated. Moreover, intent-to-treat analysis showed significant improvement in psychometric variables. In all patients prolactin levels increased during treatment, probably due to an active metabolite with weak dopamine-2-receptor antagonistic effects. No major side effects occurred, and in particular, no EPMS symptoms were seen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050323
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  • 4
    Electronic Resource
    Electronic Resource
    Savoxepine: invalidation of an “atypical” neuroleptic response pattern predicted by animal models in an open clinical trial with schizophrenic patients (1991)
    Springer
    Psychopharmacology 103 (1991), S. 280-283 
    Details
    ISSN: 1432-2072
    Keywords: Savoxepine ; Potential “atypical” neuroleptic ; Schizophrenia ; Extrapyramidal side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The new tetracyclic compound savoxepine exhibits potent antidopaminergic effects with preferential activity in the hippocampus as compared to striatum in rat brain. As a result of behavioural animal models and regional differences in dopamine receptor binding characteristics, it has been suggested to possess an “atypical” neuroleptic response pattern. In an open clinical trial, savoxepine was administered to 12 in-patients suffering from paranoid schizophrenia and schizophreniform disorder (DSM-III). Eight patients were treated with a stable dose of 0.5 mg per day throughout the study, while in the remaining patients higher doses up to 20 mg/day were administered. Mean total BPRS scores and subscores demonstrated a moderate improvement of mainly positive schizophrenic symptoms. In contrast to animal test results, savoxepine in a broad dose range produced typical untoward extrapyramidal symptoms in the majority of patients. Our results indicate that savoxepine may not possess the expected “atypical” neuroleptic response pattern, and that the predictive validity of the animal models in question used to separate antipsychotic effects from extrapyramidal reactions may be ill-founded.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244218
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    Paper (German National Licenses)
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