Digitalis-like pregnanes. Cardiac and renal effects of a glycoside of 14 beta-hydroxyprogesterone.
The synthesis of the glucoside, 3 beta-[(beta-D-glucopyranosyl)oxy]-14-hydroxy-14 beta-pregn-4-en-20-one, a 14 beta-hydroxyprogesterone glucoside (14 beta-OHP-glu), is described. This compound has an IC50 of 1 microM in a [3H]ouabain binding assay, and is about 10 times more potent than the aglycone. Like 14 beta-hydroxyprogesterone, the glucoside enhances contractility of isolated cardiac muscle. 14 beta-OHP-glu or ouabain, when infused at comparable doses into the renal artery of the anesthetized rat, markedly increases urine volume. Whereas ouabain significantly enhances urinary potassium excretion with little or no effect on sodium excretion, 14 beta-OHP-glu promotes a marked natriuresis with no significant effect on potassium excretion.
Templeton
J F
JF
Faculty of Pharmacy, University of Manitoba, Winnipeg, Canada.
Kumar
V P
VP
Bose
D
D
Smyth
D D
DD
Kim
R S
RS
LaBella
F S
FS
D000818:Animals; D004071:Digitalis Glycosides / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006908:Hydroxyprogesterones / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011188:Potassium / Q000652:urine; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011955:Receptors, Drug / Q000378:metabolism; D012964:Sodium / Q000652:urine; D000254:Sodium-Potassium-Exchanging ATPase
D004071:Digitalis Glycosides; D006908:Hydroxyprogesterones; D011955:Receptors, Drug; C028996:cardiac glycoside receptors; C053404:14-hydroxyprogesterone; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium