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  • 1
    Electronic Resource
    Electronic Resource
    Asymmetric oxygenation of chiral imide enolates. A general approach to the synthesis of enantiomerically pure .alpha.-hydroxy carboxylic acid synthons (1985)
    s.l. : American Chemical Society
    Journal of the American Chemical Society 107 (1985), S. 4346-4348 
    Details
    ISSN: 1520-5126
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/ja00300a054
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and pharmacodynamics of the ergot derivative, transdihydrolisuride, in man (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 335-339 
    Details
    ISSN: 1432-1041
    Keywords: transdihydrolisuride ; dopamine agonist ; pharmacokinetics ; pharmacodynamics ; prolactin levels ; side-effects ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma levels and urinary excretion of the dopamine agonist, transdihydrolisuride (TDHL), were measured by radioimmunoassay in healthy male volunteers given TDHL 50 µg i.v. and oral doses of 200, 400 and 800 µg. Plasma prolactin was also measured by radioimmunoassay. Following i.v. injection, the concentration of TDHL declined with a half-life of 37±19 min. The total clearance was 38±27 ml/min/kg and the apparent volume of distribution was 1.3±0.4 l/kg. The bioavailability of oral TDHL was proportional to the dose; after 200, 400 and 800 µg the bioavailability was 20±25%, 31±24% and 48±26%. TDHL was almost totally metabolized and less than 0.5% of the dose was excreted unchanged in urine in 24 h. Plasma prolactin levels were depressed by 66±15%, 75±11% and 80±7% after TDHL 200 µg, 400 µg and 800 µg. The effect lasted for more than 12 h after the lowest dose and for more than 24 h after 400 and 800 µg. Side effects, mainly nausea and headache, only occurred at the two highest dose levels.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542171
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  • 3
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and endocrine effects of terguride in healthy subjects (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 609-615 
    Details
    ISSN: 1432-1041
    Keywords: Terguride ; partial dopamine agonist ; pharmacokinetics ; endocrine effects ; pituitary hormones ; 6β-OH cortisol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma levels of the partial dopamine agonist, terguride, were measured by RIA in healthy volunteers after a single i. v. dose of 50 μg and on the first and seventh day of an oral treatment with 250 μg, 500 μg and 750 μg b. d. Basal and releasing hormone (TRH, GHRH, CRF, LHRH) — stimulated pituitary hormone secretion (PRL, TSH, GH, FSH, LH) and cortisol were also determined by RIA. Following the i. v. injection, plasma terguride levels declined biphasically, with half-lives of 0.2 and 1.5 h; total clearance was 17 ml·min−1·kg−1. the oral bioavailability of terguride over all doses was about 20%. Basal and TRH-stimulated prolactin levels were dose-dependently depressed, but the secretion of other hormones remained unaffected. Tolerance of terguride was excellent and there was no negative effect on performance or mood, nor on mixed-function oxygenase activity, assessed as urinary 6β-OH cortisol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278591
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  • 4
    Electronic Resource
    Electronic Resource
    A Novel Preparation of Scalemic N-Methyl-.alpha.-Amino Acids (1995)
    s.l. : American Chemical Society
    The @journal of organic chemistry 60 (1995), S. 4986-4987 
    Details
    ISSN: 1520-6904
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/jo00121a014
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  • 5
    Electronic Resource
    Electronic Resource
    Cognitive enhancing properties of antagonist B-carboline: New insights into the clinical research on the treatment of dementias? (1989)
    Springer
    Journal of neural transmission 1 (1989), S. 52-53 
    Details
    ISSN: 1435-1463
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02312231
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  • 6
    Electronic Resource
    Electronic Resource
    The role of D-1 and D-2 receptors (1980)
    [s.l.] : Nature Publishing Group
    Nature 286 (1980), S. 157-159 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Many dopamine agonists and antagonists have selective actions on D-l and D-2 systems, as determined by adenylate cyclase stimulation4'6 and membrane binding studies7^9, but examination of possible differences in motor, hormonal and other behavioural effects of these compounds in man has proved ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/286157a0
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  • 7
    Electronic Resource
    Electronic Resource
    Changes in noradrenaline plasma levels and behavioural responses induced by benzodiazepine agonists with the benzodiazepine antagonist Ro 15-1788 (1986)
    Springer
    Psychopharmacology 90 (1986), S. 351-357 
    Details
    ISSN: 1432-2072
    Keywords: Flunitrazepam ; Lormetazepam ; Ro 15-1788 ; Precipitated withdrawal ; Noradrenaline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Noradrenaline (NA) plasma levels were examined in 18 healthy volunteers on 2 consecutive days after a single treatment with either lormetazepam (0.06 mg/kg) (LMZ group), flunitrazepam (0.03 mg/kg) (FNZ group) or placebo (PLA group) in combination with the benzodiazepine (BZ) antagonist Ro 15-1788 (0.1 mg/kg). Behavioural responses (mood changes, anxiety) were also investigated in parallel. Both BZ decreased NA plasma levels to 50% of the basal values 10 min after the injection; administration of Ro 15-1788 15 min later reinstated NA plasma levels to basal values. A second administration of Ro 15-1788 (0.1 mg/kg) 24 h after BZ or PLA treatment increased NA plasma levels, estimated 10 min after the injection in both the LMZ- and the FNZ groups, but not in the PLA group. Behavioural responses measured under the same treatment also indicated minor anxiety responses followed by mood impairment. These data suggest that a stressful situation may be precipitated by the antagonist Ro 15-1788 24 h after a single BZ treatment, which resembles a withdrawal response, and increases NA plasma levels.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00179190
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  • 8
    Electronic Resource
    Electronic Resource
    Amnestic effects of lormetazepam and their reversal by the benzodiazepine antagonist Ro 15-1788 (1987)
    Springer
    Psychopharmacology 93 (1987), S. 507-514 
    Details
    ISSN: 1432-2072
    Keywords: Anterograde amnesia ; Lormetazepam ; Retrograde memory facilitation ; Ro 15-1788 ; Visual and auditory memory tests
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A combined visual (pictures) and auditory (word lists) memory test developed to trace the course of information processing under pharmacological or other influences was validated in a group of 20 subjects (control group) and then applied to determine the amnesic effects of lormetazepam and the reversal of these effects by the benzodiazepine antagonist Ro 15-1788. Three groups of n=10 subjects received either 0.02 mg/kg IV lormetazepam (groups B and C) or placebo (group A) followed 14 min later by 0.03 mg/kg IV Ro 15-1788 (groups A and C) or placebo (group B). The time course of memory performance in the three groups was investigated and compared across three consecutive 14-min phases: before (phase 1) and after (phase 2) the first intravenous administration, and after the second treatment (phase 3). Results were also compared with those of 20 subjects from a drug-free control group in order to verify the memory test. Lormetazepam clearly impaired immediate and delayed free recall as well as recognition in both visual and auditory tasks. These effects were completely reversed by Ro 15-1788, which alone had no clear effect on memory performance in this study. Psychometric scales indicated concomitant sedation and impaired concentration after lormetazepam alone. Interestingly, lormetazepam retrogradely enhanced performance in the visual test of delayed free recall. The impaired acquisition of new information after the administration of lormetazepam may be associated with an improvement of the consolidation process of information acquired before drug treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00207244
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  • 9
    Electronic Resource
    Electronic Resource
    Human studies on the benzodiazepine receptor antagonist β-carboline ZK 93 426: preliminary observations on psychotropic activity (1987)
    Springer
    Psychopharmacology 93 (1987), S. 421-427 
    Details
    ISSN: 1432-2072
    Keywords: ZK 93 426 ; β-carboline ; BZ receptor antagonist ; Behavioural changes ; Pharmacokinetics ; Humans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The β-carboline ZK 93 426, a benzodiazepine receptor antagonist, was administered intravenously to human volunteers at two different doses (0.01 mg/kg, 0.04 mg/kg) according to a double-blind, placebo controlled design. Vital functions (i.e. blood pressure, heart rate, ECG, EEG), peripheral (finger) skin temperature and performance in psychometric tests for psychotropic and cognitive effects were evaluated. Blood samples were collected in addition and certain pharmacokinetic parameters were estimated. ZK 93 426 in both doses was well tolerated and exhibited no side effects. A decrease in peripheral skin temperature and heart rate was observed. In a general estimation of behavioural changes, volunteers experienced a stimulant and activating effect of the drug. An improvement in performance was observed in two cognitive tasks, the “logical reasoning task” and “pictures differences task” which estimated concentration and attention, respectively. No effects were found in time estimation. Plasma levels 5 min after intravenous administration of ZK 93 426 were 16±10 ng/ml and 52±31 ng/ml for 0.01 mg/kg and 0.04 mg/kg, respectively. Total clearance was calculated as 46±22 ml/min/kg (0.04 mg/kg).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00207229
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  • 10
    Electronic Resource
    Electronic Resource
    Human studies on the benzodiazepine receptor antagonist β-carboline ZK 93 426: antagonism of lormetazepam's psychotropic effects (1988)
    Springer
    Psychopharmacology 95 (1988), S. 463-471 
    Details
    ISSN: 1432-2072
    Keywords: Lormetazepam ; ZK 93 426 ; Multiple sleep latency test ; Vigilosomnogram ; Cognitive functions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of lormetazepam (0.03 mg/kg IV) a benzodiazepine (BZ) derivative in combination with ZK 93 426 (0.04 mg/kg IV) a β-carboline, benzodiazepine receptor antagonist were evaluated in humans. Independently, the effects of ZK 93 426 on its own were investigated. A psychometric test battery to evaluate sedation (visual analog scales (VAS), anxiolysis (state-trait-anxiety inventory scale (STAIG X1) and cognitive functions [logical reasoning test (LR), letter detection test (LD)] was applied before and several hours after initiation of treatment. Multiple sleep latency test (MSLT), which measures day time sleepiness, was also applied. Vigilosomnograms analysed from standard EEG recordings were evaluated shortly before and for 1 h after treatment. Treatment started with an intravenous injection of either lormetazepam (LMZ) or placebo (PLA), which was followed 30 min later by administration of either ZK 93 426 or placebo; thus four treatment groups were created (PLA + PLA, LMZ + PLA, LMZ + ZK 93 426 and PLA + ZK 93 426). ZK 93 426 antagonized the sedative and hypnotic effect of LMZ as estimated by MSLT and vigilosomnograms, respectively. Impairment of cognitive functions (LR and LD) induced by LMZ was also antagonized by ZK 93 426. ZK 93 426 had no effect on the changes in the time estimation seen in the LMZ group. Furthermore, ZK 93 426 on its own increased vigilance (alertness) as measured by the vigilosomnogram. A competitive antagonism at the benzodiazepine binding site between ZK 93 426 and LMZ is suggested by their combination effects; the intrinsic activity of ZK 93 426 seems to be due to its weak partial inverse agonist component.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00172956
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