屈:孕激素和antimineralocorticoid antiandrogenic活动。
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Muhn P,福尔曼U, Fritzemeier KH Krattenmacher R,书评E
屈:孕激素和antimineralocorticoid antiandrogenic活动。
安N Y科学。1995年6月12日;761:311-35。doi: 10.1111 / j.1749-6632.1995.tb31386.x。
- PubMed ID
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7625729 (在PubMed]
- 文摘
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屈(ZK 30595;6β,7β,15β,16 beta-dimethylen-3-oxo-17 alpha-pregn-4-ene-21, 17-carbolactone)是一种新型的孕激素在临床开发。其特点是一个创新的药效学资料非常的孕激素密切相关。潜在的应用包括口服避孕药,激素替代疗法和治疗内分泌失调。屈的药理特性进行体外受体结合和transactivation实验和体内适当的动物模型。与孕激素在定性协议,强烈的复合结合孕激素和盐皮质激素受体和雄激素和糖皮质激素受体的亲和力较低。没有可检测雌激素受体结合。孕激素类固醇激素格斗和敌对活动,其在transactivation比较实验。个人类固醇激素受体是一起人为表达报告基因在适当的细胞系。激素都是无法产生任何雄激素受体介导争胜活动。 Rather, both progesterone and drospirenone distinctly antagonized androgen-stimulated transcriptional activation. Likewise, both compounds only very weakly activated the mineralocorticoid receptor but showed potent aldosterone antagonistic activity. Drospirenone did not induce glucocorticoid receptor-driven transactivation. Progesterone was a weak agonist in this respect. Drospirenone exerts potent progestogenic and antigonadotropic activity which was studied in various animal species. It efficiently promotes the maintenance of pregnancy in ovariectomized rats, inhibits ovulation in rats and mice and stimulates endometrial transformation in the rabbit. Furthermore, drospirenone shows potent antigonadotropic, i.e., testosterone-lowering activity in male cynomolgus monkeys. The progestogenic potency of drospirenone was found to be in the range of that of norethisterone acetate. The majority of clinically used progestogens are androgenic. Drospirenone, like progesterone, has no androgenic but rather an antiandrogenic effect. This property was demonstrated in castrated, testosterone propionate substituted male rats by a dose-dependent inhibition of accessory sex organ growth (seminal vesicles, prostate). In this model, the potency of drospirenone was about a third that of cyproterone acetate. Drospirenone, like progesterone, shows antimineralocorticoid activity, which causes moderately increased sodium and water excretion. This is an outstanding characteristic which has not been described for any other synthetic progestogen before. Drospirenone is eight to ten times more effective in this respect than spironolactone. The natriuretic effect was demonstrable for at least three weeks upon daily treatment of rats with a dose of 10 mg/animal. Drospirenone is devoid of any estrogenic, glucocorticoid or antiglucocorticoid activity. In summary, drospirenone, like progesterone, combines potent progestogenic with antimineralocorticoid and antiandrogenic activity in a similar dose range.(ABSTRACT TRUNCATED AT 400 WORDS)