Reference

Progestogens with antimineralocorticoid activity

Progestogens with antimineralocorticoid activity. Losert, W.; Casals-Stenzel, J.; Buse, M. (Res. Lab., Schering A.-G., Berlin D-1000/65, Fed. Rep. Ger.). Arzneim.-Forsch., 35(2), 459-71 (English) 1985. CODEN: ARZNAD. ISSN: 0004-4172. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) Eleven progestogenic steroids were tested for their ability to inhibit the renal actions of aldosterone in rats. Gestodene [60282-87-3] (26.7 or 53.3 mg/kg, s.c.), progesterone [57-83-0] (53.3 mg/kg, s.c.), spironolactone [52-01-7] (26.7 mg/kg, s.c.), spirorenone [74220-07-8] (13.3 mg/kg, s.c.), 1,2-dihydrospirorenone [67392-87-4] (13.3 mg/kg, s.c.), and 1,2a-methylene-spirotenone [95218-20-5] (13.3 mg/kg, s.c.) all exhibited marked antimineralocorticosteroid activity. Canrenone [976-71-6] (53.3 mg/kg, s.c.) had weak activity, whereas d-norgestrel [6533-00-2], norethisterone acetate [51-98-9], 3-keto-desogestrel [54048-10-1], and cyproterone acetate [427-51-0] were inactive in this test. With the exception of progesterone, the antimineralocorticosteroid activity of the steroids tested was also demonstrated after oral administration. The potencies, relative to spironolactone, were: gestodene, ~0.2; canrenone, ~0.3-0.35; spirorenone, 7-8; 1,2-dihydrospirorenone, ~8; 1,2a-methylene-spirorenone, ~3.5. Gestodene may be regarded as the 1st progestogen of the nortestosterone series exhibiting a more natural, progestogen-like activity; however, its low antimineralocorticosteroid potency precludes its therapeutic usefulness in man. In contrast, 1,2-dihydrospirorenone exhibit progestogenic and antimineralocorticosteroid activity in the same dose range and may be the prototype of a new class of orally active progestogens with progesterone-like effects on salt and water excretion.

Additive effect of drospirenone/17b-estradiol in hypertensive postmenopausal women receiving enalapril

Additive effect of drospirenone/17b-estradiol in hypertensive postmenopausal women receiving enalapril. Preston, Richard A.; Alonso, Alberto; Panzitta, Darlene; Zhang, Paul; Karara, Adel H. (Division of Clinical Pharmacology Clinical Research Center, Department of Medicine, University of Miami School of Medicine, Miami, FL, USA). American Journal of Hypertension, 15(9), 816-822 (English) 2002 Elsevier Science Inc. CODEN: AJHYE6. ISSN: 0895-7061. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) Section cross-reference(s): 1 Aldosterone has been implicated in the pathogenesis of progressive cardiovascular disease. Drospirenone (DRSP) is a novel progestin with aldosterone receptor antagonist activity developed for hormone replacement therapy (HRT) as DRSP/17b-estradiol (DRSP/E2). The authors investigated the additive effect of DRSP/E2 vs. placebo on 24-h ambulatory blood pressure (BP) in postmenopausal women with hypertension treated with enalapril maleate (ENA). This was a double-blind, randomized, two-parallel group trial. Twenty-four nonsmoking postmenopausal women receiving 10 mg of ENA twice a day before study were randomized to DRSP/E2 + ENA or placebo (P) + ENA for 14 days. Twenty-four-hour ambulatory BP, plasma renin activity, and serum aldosterone were detd. at baseline and on day 14. Compared to placebo, 24-h mean BP in the DRSP/E2 + ENA group decreased significantly from baseline (139/80 mm Hg), systolic (-9 mm Hg) and diastolic (-5 mm Hg). Essentially no change from baseline (139/83 mm Hg) in systolic or diastolic 24-h ambulatory BP were obsd. in the P + ENA group. Aldosterone (mean [SD]) increased from baseline by 2. 75847-73-3 and 67392-87-4 which are cas registry numbers of substances are two of reagents here.6 ng/dL in the DRSP/E2 + ENA group, and decreased by 0.3 ng/dL in the P + ENA group consistent with an antimineralocorticoid effect. The authors' results suggest a significant additive BP-lowering effect of DRSP/E2 on both systolic and diastolic BP in hypertensive postmenopausal women receiving ENA, consistent with an antimineralocorticoid effect. DRSP/E2, a HRT with antimineralocorticoid effects, could offer a novel potential mechanism for reducing cardiovascular end points in postmenopausal women. .