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  • 1
    Electronic Resource
    Electronic Resource
    Building a competitive functional genomics platform (1999)
    [s.l.] : Nature America, Inc.
    Nature biotechnology 17.1999, 1s, BE18-, (2 S.) 
    Details
    ISSN: 1546-1696
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: [Auszug] Translating genomic data into knowledge for therapeutic discovery requires a well-developed and well-managed ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/4631
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Biochemical and pharmacological effects of fluperlapine on noradrenaline and acetylcholine systems in some rodent, bovine and crustacean preparations (1986)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 332 (1986), S. 357-363 
    Details
    ISSN: 1432-1912
    Keywords: Fluperlapine ; Noradrenaline reuptake inhibition ; α1-adrenoceptor blockade ; Anticholinergic effects ; Antischizophrenic effects ; Antidepressant effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fluperlapine was compared with clozapine, chlorpromazine, haloperidol and imipramine regarding its effects on some cholinergic and noradrenergic animal systems. Fluperlapine and clozapine showed the most pronounced anticholinergic effects. Fluperlapine was equipotent with clozapine in displacing [3H]-QNB from muscarinic receptors of the calf cerebral cortex (IC50 about 15 nM). In the mydriasis test in the mouse and in the crayfish hindgut bioassay the differences between fluperlapine and clozapine were small. Like the other antischizophrenic drugs tested, fluperlapine displayed a marked affinity for α1-adrenoceptors (calf cerebral cortex: IC50 about 10 nM) but a neglible affinity for α2-adrenoceptors in the same tissue. Only clozapine showed a weak affinity for the latter receptor type. Fluperlapine was as effective as imipramine in antagonizing tetrabenazine-induced ptosis in the rat, the antiptotic effect remaining constant after up to ten daily drug administrations. Still, imipramine was stronger than fluperlapine as an inhibitor of the accumulation of [3H]-noradrenaline ([3H]-NA) in rat cerebral cortex slices. Fluperlapine's effects on the spontaneous and the electrically-induced release of [3H]-NA from rat cerebral cortex slices, with and without protriptyline, showed it to be an inhibitor of the reuptake of NA. The results indicate that the pharmacological profile of fluperlapine is similar to that of clozapine, with additional antidepressant properties.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00500087
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  • 3
    Electronic Resource
    Electronic Resource
    In situ situation (1992)
    [s.l.] : Nature Publishing Group
    Nature 356 (1992), S. 470-470 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] SIR- In a recent issue of Nature (355, 163; 1992), we were attracted by the title of a paper, "Rapid-time-course miniature and evoked excitatory currents at cerebellar synapses in situ", especially as we were looking forward to welcoming new members to the otherwise ever-shrinking club of people ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/356470b0
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  • 4
    Electronic Resource
    Electronic Resource
    Effects of clozapine in a selective muscarinic bioassay and on single cells of the rat hippocampus (1982)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 320 (1982), S. 20-25 
    Details
    ISSN: 1432-1912
    Keywords: Bioassay ; Muscarinic receptor ; Clozapine ; Iontophoresis ; Hippocampus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Acetylcholine was applied to isolated crayfish hindguts and caused dose-dependent increases in its contractile force. These effects were blocked by muscarinic but not by nicotinic antagonists. Dopamine, noradrenaline, enkephalin or GABA agonists had either no effect or one distinct from the action of acetylcholine. Of a number of antischizophrenic drugs, clozapine had the strongest antimuscarinic action with a pA2 value of 7.5, followed by thioridazine with a pA 2 value of 6.7. All other drugs of the phenothiazine, butyrophenone or benzamide type were ineffective. From these results, it was concluded that the crayfish hindgut is a very reliable and simple bioassay for muscarinic actions of drugs. Clozapine was also applied by microiontophoresis to cat hippocampal neurons and its effects on carbachol-, acetylcholine-and glutamate-induced excitations was assessed. It displayed an inhibitory action on excitations induced by the cholinergic agents, but did not visibly affect those induced by glutamate. The fact that clozapine had strong antimuscarinic effects on the crayfish hindgut as well as on hippocampal neurons of a mammalian indicates a similarity between the muscarinic receptors in both tissues.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00499066
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  • 5
    Electronic Resource
    Electronic Resource
    Synthesis and N-Methyl-D-aspartate (NMDA) Antagonist Properties of the Enantiomers of α-Amino-5-(phosphonomethyl)[1,1′-biphenyl]-3-propanoic Acid. Use of a New Chiral Glycine Derivative (1992)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 75 (1992), S. 855-864 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The enantiomers of the title compound, 7a and ent-7a, and of substituted analogues are synthesized. The absolute configuration of 7a is deduced from that of (tert-butyl 2-tert-butyl)-3-methyl-4-oxoimidazolidin-1-carboxylate (15) and from the trans-configuration of the intermediate 17a which in turn is assigned on the basis of 1H-NMR nuclear Overhauser effect (NOE) measurements. Instead of 15, the 2-isopropyl-substituted analogue 21 can also be employed. Its preparation from glycine, methylamine, isobutyraldehyde, and (Boc)2O, and the resolution through the bis-O,O′-(4-toluyl)tartrate salt 20 are described. In two functional tests (rat neocortical slice and frog hemisected spinal cord preparation) the (S)-enantiomer 7a (SDZ EAB 515) is shown to be a very potent, selective competitive NMDA antagonist.
    Additional Material: 10 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19920750320
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  • 6
    Electronic Resource
    Electronic Resource
    Synthesis and NMD A Antagonistic Properties of the Enantiomers of 4-(3-phosphonopropyl)piperazine-2-carboxylic acid (CPP) and of the unsaturated analogue (E)-4-(3-phosphonoprop-2-enyl)piperazine-2-carboxylic acid (CPP-ene) (1989)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 72 (1989), S. 1043-1051 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The (R)- and (s)-enantiomers of 4-(3-phosphonopropyl)piperazine-2-carboxylic acid (D- and L-CPP, resp.; 15 and 16, resp.), and of its unsaturated analogue (E)-4-(3-phosphonoprop-2-enyl)piperazine-2-carboxylic acid (D- and L-CPP-ene, resp.; 13 and 14, resp.) were prepared. The absolute configuration of the enantiomers was determined by a chemical correlation of the menthyl ester 7 with D-asparagine. The affinity of these derivatives for the NMDA receptor was determined by displacement of [3H]CPP in rat cerebral cortical membranes. In two functional tests (the frog hemisected spinal cord preparation and the sodium efflux test from rat brain slices), D-CPP-ene appears to be the most potent, enantiomerically pure, competitive NMDA antagonist known to date.
    Additional Material: 2 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19890720522
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