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  • Title: [14,15-beta-oxido analog of proscillaridin (HOE 040). A new cardiac glycoside with low arrhythmic activity and greater absorption ratio].
    Author: Lindner E, von Reitzenstein G, Schöne HH.
    Journal: Arzneimittelforschung; 1979; 29(2):221-6. PubMed ID: 109100.
    Abstract:
    The 14,15-beta-oxido analogue of proscillaridin A (HOE 040), in a dose 4 times higher showed equally positive-inotropic effect on the isolated guinea pig heart as did proscillaridin A. In the dog in vivo HOE 040 was equally positive-inotropic, as measured by the increase of dp/dt of the left ventricle of the heart, as proscillaridin A. In combination with aconitine, HOE 040 also in 4fold higher dose caused less cardiac fibrillation on the isolated guinea pig heart than did proscillaridin A. The dose of HOE 040 which by infusion in the guinea pig in vivo precipitates cardiac arrhythmias was 4 times higher than that of proscillaridin A, the lethal dose was 5 times higher. In dogs in vivo the dose of HOE 040 by infusion causing prolongation of PQ or cardiac arrhythmias, resp., was twice the dose necessary of proscillaridin A, the lethal dose was nearly 5 times higher. The decrease of cardiac activity in Rhesus monkeys amounted to 69% in 24 h, whereas proscillaridin A decreased cardiac activity only by 41% in 24 h. The absorption of HOE 040 from the duodenum of dogs anesthetized with pentobarbital amounted to 72%, whereas proscillaridin A is observed by only between 14 and 25%. The concentration of the drug HOE 040 in hearts of rats was twice, in the hearts of dogs 3 fold that of proscillaridin A. The concentrations of both drugs in the brain of rats and dogs were not different. In the biochemical test system in vitro the blocking effect of both drugs on the Na+K+-ATPase of ox brain was not different.
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