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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. [ABSTRACT FROM AUTHOR]

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), 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. [ABSTRACT FROM AUTHOR]

The cardioprotective effects of mioflazine, a recently developed cardiovascular drug, were investigated in 41 anaesthetised open chest Beagle dogs subjected to 1 h normothermic global myocardial ischaemia. The severity of the model is evidenced by the finding that only one out of 20 control dogs could be weaned from extracorporeal bypass. Oral pretreatment with mioflazine (2.5 mg·kg−1) resulted in complete functional recovery in 17 out of 20 animals. Biochemical analysis of left ventricular biopsies taken before, during and after aortic cross clamping showed a preservation of purines and a better recovery of ATP, ATP/ADP × Pi ratio and energy charge (p<0.05) in the pretreated animals. Morphological and cytochemical assessment of the myocardium demonstrated that the ultrastructure of the sarcolemma and its calcium binding capacity is remarkably well preserved in the drug treated animals. These results indicate a strong cardioprotective effect of mioflazine. The biochemical, cytochemical and ultrastructural findings suggest an interaction of the drug with the sarcolemma. [ABSTRACT FROM PUBLISHER]