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  • 1
    Electronic Resource
    Electronic Resource
    Steroid Effects on Central Neurons and Implications for Psychiatric and Neurological Disorders (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 746 (1994), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1994.tb39255.x
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  • 2
    Electronic Resource
    Electronic Resource
    Sleep Endocrine Effects of Megestrol Acetate in Healthy Men (1998)
    Oxford, UK : Blackwell Science Ltd
    Journal of neuroendocrinology 10 (1998), S. 0 
    Details
    ISSN: 1365-2826
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Synthetic and naturally occurring steroids exert a variety of neural effects that include modulation of nocturnal sleep. The present study focuses on the effect of progesterone receptor (PR) activation on the nocturnal sleep electroencephalogram (EEG) in male volunteers. As a PR ligand, the synthetic progesterone megestrol was used, which has the advantage over progesterone in that it is not metabolized into other steroid compounds which could cloud the progesterone-mediated effects through their own neuroactive properties. Nine healthy male volunteers were investigated in a prospective single-blind randomized study design. They received either placebo tablets or megestrol acetate dosages of 160, 320 or 480 mg at 14.00 h and 19.00 h. Blood samples were drawn half-hourly from 22.00 h until 07.00 h. After 320 mg megestrol, plasma adrenocorticotropin secretion was lower and growth hormone secretion was higher than after 160 mg and 480 mg megestrol or placebo. Similarly, the reduction in the relative amount of rapid eye movement sleep was most pronounced after 320 mg. Thus, progesterone receptor activation, as reflected by the sleep EEG and associated pituitary hormone secretion, follows a nonlinear U-shape dose dependency of a well-defined PR ligand, which may explain the unresolved inconsistencies of neuroendocrine progesterone effects to date. Moreover, employing a CV1 cell line, contransfected with a human glucocorticoid receptor expression vector and a reporter gene-based detection system for transcriptional activity, revealed that a PR agonist such as megestrol may also activate glucocorticoid receptors. This may account for some of the neuroendocrine effects of megestrol and other progestins.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2826.1998.00259.x
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  • 3
    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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  • 4
    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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  • 5
    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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  • 6
    Electronic Resource
    Electronic Resource
    Opioid activities of human β-casomorphins (1985)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 331 (1985), S. 351-354 
    Details
    ISSN: 1432-1912
    Keywords: Human β-casein ; Opioid peptides ; Opioid receptor ligands ; Human β-casomorphins ; Computerized binding data analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Opioid activities of human β-casomorphin-4,-5,-7 and -8 and, for comparison, of the corresponding bovine β-casomorphins were studied in the guinea-pig ileum preparation. Binding parameters, i.e. K d -values and binding site concentrations, for the interaction of human and bovine β-casomorphins with opioid receptors in rat brain homogenates were determined in inhibition experiments, using [3H]-(d-Ala2, MePhe4, Gly-ol5)enkephalin, [3H]-(d-Ala2, d-Leu5)enkephalin and [3H]ethylketazocin as μ-, δ- and κ-opioid receptor ligands. Analysis of binding data was performed using a non-linear curve fitting program. All β-casomorphins examined displayed opioid activity. The affinity was highest for μ-receptors, less so for δ-receptors and lowest for κ-receptors. It is suggested that human β-casomorphins might play a role as “food hormones”.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00500818
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  • 7
    Electronic Resource
    Electronic Resource
    Determination of β-Endorphin and Fragments Thereof in Human Plasma Using High-Performance Liquid Chromatography and a Multiple Radioimmunoassay System (1986)
    Springer
    Pharmaceutical research 3 (1986), S. 142-149 
    Details
    ISSN: 1573-904X
    Keywords: β-endorphin in human plasma ; multiple β-endorphin immunoreactive materials ; HPLC of peptides ; multiple radioimmunoassay system ; peptide region specific radioimmunoassays
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A method for the determination of β-endorphin and β-endorphin fragments in human plasma was developed. β-Endorphin-related peptides were extracted from plasma using octadecasilyl-silica cartridges. Extracts were subjected to re versed-phase high-performance liquid chromatography (HPLC). Extracts as well as HPLC column eluates were assayed using a multiple radioimmunoassay system; several antibodies directed against various distinct regions of the β-endorphin molecule were employed. Using this method, evidence for the presence of multiple β-endorphin fragments in the plasma of healthy young volunteers (under normal conditions) was obtained.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016357806879
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