Comparative hemodynamic study of a new aminosteroid: LND-623 with its 20 alpha-isomer: LND-369, and with digoxin and digoxigenin-rhamnoside in the anesthetized dog.
Hemodynamic effects of LND-623, a new aminosteroid lacking the C17 lactone ring and the C14 hydroxyl group common to the natural glycosides, were studied in the pentobarbital-anesthetized dog and compared to those of its 20 alpha-isomer LND-369 and of digoxin and digoxigenin-rhamnoside (DRh). Twenty-four mongrel dogs were divided into 4 groups. Group I received either LND-623 or saline on study day 1 and the other drug or saline 1 wk later. Saline was replaced by digoxin in group II, digoxigenin-rhamnoside in group III, and LND-369 in group IV. All drugs except LND-369 were infused as 3.10(-9) mol.kg-1.min-1 over 20 minutes. LND-369 was infused at twice the dose. LND-623 increased left ventricular dP/dt for at least 3 h with a peak at end-infusion or 15 min later, accompanied by a transient vasopressor effect. LND-369 induced, at twice the dose, an inotropic effect of comparable magnitude but of shorter duration. Inversely, it provoked a more marked and prolonged vasopressor effect than its 20 beta-isomer, LND-623. Maximal digoxin inotropic effect occurred later but was of comparable magnitude to that induced by LND-623. Its vasopressor effects reached a plateau rapidly and remained sustained until min 200. Digoxigenin-rhamnoside inotropic but not vasopressor effects are weaker than those of LND-623. It is concluded that LND-623, although lacking the most common structural features of the natural cardiac glycosides, provoked rapid and sustained inotropic activities with transient vasopressor effects. These time-course effects differ from digoxin, and these differences are unrelated to their sugar-moiety characteristics. LND-623 inotropic effect is twice as potent as its 20 alpha-isomer.
Weissenburger
J
J
Laboratoire de Pharmacologie, Faculté de Médecine Saint-Antoine, Paris, France.
Heckle
J
J
Biour
M
M
Poirier
J M
JM
Jarreau
F X
FX
Jaillon
P
P
Cheymol
G
G
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004076:Digoxigenin / Q000494:pharmacology*; D004077:Digoxin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004285:Dogs; D006027:Glycosides / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007536:Isomerism; D008362:Mannosides / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D011278:Pregnanes / Q000494:pharmacology*; D012083:Renin / Q000097:blood
D006027:Glycosides; D008362:Mannosides; D011278:Pregnanes; D004077:Digoxin; C045251:LND 623; D012083:Renin; D004076:Digoxigenin