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  • 1
    Electronic Resource
    Electronic Resource
    Sleep improvement in dogs after oral administration of mioflazine, a nucleoside transport inhibitor (1987)
    Springer
    Psychopharmacology 91 (1987), S. 434-439 
    Details
    ISSN: 1432-2072
    Keywords: Mioflazine ; EEG ; Sleep-wakefulness ; Nucleoside transport inhibitor ; Adenosine ; Dog
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mioflazine, a nucleoside transport inhibitor, was given PO to dogs at doses of 0.04–10 mg/kg. Sixteen hour polygraphic sleep recordings were made and analysis and sleep stage classification was done by computer. Mioflazine decreased wakefulness and increased slow wave sleep, but did not affect the latencies of either REM sleep or slow wave sleep. This increased sleep was due to an increase in the number of light and deep slow wave sleep epochs. The effect lasted for about 8 h. The decreased wakefulness and increased slow wave sleep could be antagonized by the adenosine antagonist caffeine (2.5 and 10 mg/kg, PO); however, there was not a pure antagonistic effect. It might be that the enhancement of slow wave sleep is due to an activation of brain adenosine receptors. This is the first report of a drug acting on adenosine that given orally improves sleep. Mioflazine might be the prototype of substances worth considering for the treatment of a variety of sleep disorders.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00216007
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Formation and release of nucleosides in the ischemic myocardium. Is the guinea-pig the exception? (1985)
    Springer
    Basic research in cardiology 80 (1985), S. 653-660 
    Details
    ISSN: 1435-1803
    Keywords: Myocardial ischemia ; nucleosides ; nucleosidetransport inhibition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In this study evidence is provided to suggest that nucleoside formation with hypoxia in myocardial tissue from the guinea-pig follows a different course from that in the rat, rabbit or dog. 1) After ischemia, tissue levels of adenosine remain barcly detectable in the guinea-pig but rise considerably in the rat and the dog. 2) IMP, remaining almost absent in the dog, does not change in the rat but strongly increases (×6) in the guinea-pig heart with ischemia. 3) Mioflazine, a nucleoside transport inhibitor, completely reverses the ratio adenosine/inosine in dog myocardium after 8 min of ischemia, making adenosine by far the major nuclcoside. No effect could be detected in the guinea-pig. 4) In contrast with the rat and rabbit, ischemia in the guinea-pig does not lead to any considerable release of adenosine upon reperfusion. 5) In the rabbit, the presence of a nucleoside transport inhibitor completely reverses the adenosine/inosine ratio in reperfusates after ischemia. Although the release is strongly inhibited under these conditions in the guinea-pig, adenosine release remains negligible when compared with inosine. 6) Even in the presence of high concentrations of an adenosine deaminase inhibitor, inosine remains the major metabolite released upon reperfusion after ischemia, in the guinea-pig heart.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01907864
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Oral pretreatment with mioflazine completely changes the pattern and remarkably prolongs the accumulation of nucleosides in ischemic and reperfused myocardium (1986)
    Springer
    Basic research in cardiology 81 (1986), S. 407-416 
    Details
    ISSN: 1435-1803
    Keywords: nucleosides ; adenosine ; mioflazine ; ischemia ; reperfusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In dog myocardium, the changes in the levels of creatine phosphate, inorganic phosphate, ATP, ADP, AMP, adenosine and inosine with 8 min of ischemia and subsequent reperfusion for 2, 4, 8, 16 and 32 min have been followed. Creatine phosphate and inorganic phosphate recovered completely within a few minutes as did the energy charge. However, total nucleotides remained depressed, the decrease being compensated for by the increase in inosine levels during ischemia. There was a rapid removal of the latter with reperfusion. Low oral doses of mioflazine (2.5 mg·kg−1), given 2.5 h before LAD occlusion, did not affect the pattern of changes seen in control animals, except for the nucleosides. The drug induced a complete reversal of the adenosine to inosine ratio during ischemia and a remarkable prolongation of the accumulation within the tissue of mainly adenosine during early reperfusion and inosine afterwards. Assuming that the main action of mioflazine is through inhibition of nucleoside transport, the present results provide interesting information about the mechanism of release, metabolism and final washout of adenosine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01907461
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    Paper (German National Licenses)
    Fulltext
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