Structure-activity relationships of an aminosugar cardiac glycoside, ASI-222 HCl, in the heart-lung preparation of the dog.
ASI-222 [3-beta-O-(4-amino-4,6-dideoxy-beta-D-galactopyranosyl) digitoxigenin HCl] is a semisynthetic aminosugar cardiac glycoside that has been shown to have a greater therapeutic index than ouabain or digoxin in dogs. We have compared the effects of ASI, digitoxigenin, digitoxigenin-beta-D-galactose, and digoxin in the dog heart-lung preparation. Minute work and stroke work were calculated. Controls were obtained before and after the hearts were failed with sodium pentobarbital. ASI-222 is about three times more potent than digitoxigenin and about twice as potent as digitoxigenin-beta-D-galactose in producing similar increases in the left ventricular stroke work. ASI-222 is about three times more potent than digoxin in creasing left ventricular stroke work. Our results indicate that the addition of an aminosugar group to the genin further increased potency over that observed with the addition of a single neutral sugar and prolonged the duration of activity in failing myocardial tissue.
D000617:Aminoglycosides / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002301:Cardiac Glycosides / Q000494:pharmacology*; D004073:Digitoxigenin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004077:Digoxin / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008168:Lung / Q000502:physiology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D013329:Structure-Activity Relationship; D013997:Time Factors
D000617:Aminoglycosides; D002301:Cardiac Glycosides; D004073:Digitoxigenin; C012114:ASI-222; D004077:Digoxin