Inotropic activity of digitoxigenin glucoside and related glycosides.
The cardiovascular effects of digitoxigenin glucoside and two derivatives, digitoxigenin glucoside tetraacetate and 4',6'-isopropylidene digitoxigenin glucoside were studied in pentobarbital-anaesthetized dogs. Digoxin (0.112 mumol/kg) and digitoxigenin glucoside (0.056 mumol/kg) produced similar increases in myocardial contractility, although digitoxigenin glucoside was faster in onset of action and had a shorter duration of action. Digitoxigenin glucoside caused a significantly greater increase in blood pressure than digoxin. Digitoxigenin glucoside tetraacetate (0.056 mumol/kg) and isopropylidene digitoxigenin glucoside (0.112 mumol/kg) also increased myocardial contractility. Time to peak effect and duration of action were similar to those of digitoxigenin glucoside. The tetraacetate derivative of digitoxigenin glucoside was less hypertensive than the parent compound. The results suggest that the rapid onset and short duration of effect are a function of the glucose moiety. The rapid onset and, what appears to be, a reduced tendency to accumulate may confer clinical potential for these analogues.
Altman
P M
PM
Department of Pharmacy, University of Sydney, Australia.
Einstein
R
R
Goodman
A H
AH
Thomas
R E
RE
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002301:Cardiac Glycosides / Q000493:pharmacokinetics / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D002855:Chromatography, Thin Layer; D004073:Digitoxigenin / Q000493:pharmacokinetics / Q000494:pharmacology*; D004077:Digoxin / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*
D002301:Cardiac Glycosides; D002316:Cardiotonic Agents; D004073:Digitoxigenin; D004077:Digoxin