Smyth D D, Templeton J F, Sashi Kumar V P, Yan Y, Widajewicz W, LaBella F S
Department of Pharmacology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Can J Physiol Pharmacol. 1992 May;70(5):723-7. doi: 10.1139/y92-095.
The synthesis of 17 alpha-acetoxy-3 beta-[(beta-D-glucopyranosyl)oxy]- 6 alpha-methylpregn-4-en-20-one, the glucoside of medroxyprogesterone acetate (MPA-glu), is described. MPA-glu and 14-amino-20 beta-hydroxy-3 beta-[(alpha-L-rhamnopyranosyl)oxy]-5 beta, 14 beta-pregnane (LND 623), pregnane glycosides that bind to the digitalis receptor, and digoxin, a cardiac glycoside, were infused intravenously into the anesthetized guinea pig. Each of the three steroids significantly enhanced urinary volume and sodium excretion without affecting blood pressure and creatinine clearance. Potassium excretion was markedly enhanced by digoxin but unaffected by MPA-glu or LND 623. These observations conform to previous work that demonstrated, in the rat, potassium-sparing diuresis by the glucoside of 14 beta-hydroxyprogesterone, a cardiotonic pregnane. There is a dissociation between potency to inhibit [3H]ouabain binding and the extra ATPase actions of the digitaloid pregnanes.
描述了醋酸甲羟孕酮的葡糖苷(MPA-葡糖)即17α-乙酰氧基-3β-[(β-D-吡喃葡萄糖基)氧基]-6α-甲基孕-4-烯-20-酮的合成。将MPA-葡糖、14-氨基-20β-羟基-3β-[(α-L-鼠李糖基)氧基]-5β,14β-孕烷(LND 623)、与洋地黄受体结合的孕烷糖苷以及强心苷地高辛静脉注入麻醉的豚鼠体内。这三种甾体中的每一种都能显著增加尿量和钠排泄,而不影响血压和肌酐清除率。地高辛能显著增加钾排泄,但MPA-葡糖或LND 623对其无影响。这些观察结果与之前在大鼠身上的研究结果一致,即强心孕烷14β-羟基孕酮的葡糖苷具有保钾利尿作用。在抑制[3H]哇巴因结合的效力与洋地黄样孕烷的额外ATP酶作用之间存在分离。