Pharmacological Profile of RU 486 in Animals
Pharmacological Profile of RU 486 in Animals
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DOI：
10.1007/978-1-4684-1242-0_3
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发表时间：
1985
期刊：
影响因子：
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通讯作者：
D. Philibert;M. Moguilewsky;I. Mary;D. Lecaque;C. Tournemine;J. Secchi;R. Deraedt
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文献类型：
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作者：
D. Philibert;M. Moguilewsky;I. Mary;D. Lecaque;C. Tournemine;J. Secchi;R. Deraedt
RU 486 是一种原始的多方面抗激素。它似乎是一种有效的孕激素和糖皮质激素拮抗剂，但即使在非常高的剂量下也没有表现出激动作用。因此，根据所用的生物测定，以3至20 mg/kg的剂量口服施用RU 486完全抑制外源孕酮对兔子子宫内膜增殖、子宫腺细胞线粒体体积密度、蜕膜形成和卵巢切除大鼠妊娠维持的影响。此外，它被证明对大鼠和小鼠具有抗诱和堕胎作用。在骑自行车的猴子中，在黄体中期给药时，它会诱发月经。作为一种抗糖皮质激素成分，RU 486 在 10M−6 时有效拮抗地塞米松对尿苷掺入大鼠胸腺细胞 RNA 和大鼠垂体细胞分泌 ACTH 的影响。在体内（对肾上腺切除大鼠的剂量为 10 mg/kg），它完全预防皮质酮和地塞米松的胸腺溶解作用；还能完全阻断地塞米松引起的尿量增加和钾排泄。在后一项测试中，其抗糖皮质激素活性可通过增加地塞米松剂量而迅速且完全逆转。使用灌注技术，我们观察到 RU 486 不会抑制 ACTH 刺激的大鼠肾上腺细胞中的皮质酮生物合成。该化合物还对精囊和前列腺重量具有中等的抗雄激素活性，比其其他两种拮抗剂特性（在大鼠中评估）弱约 20 倍。在不同物种（大鼠、兔子和小鼠）中，它表现出轻微的子宫营养活性，大约比雌二醇弱 10,000 倍；但是，与雌激素不同，它不能诱导卵巢切除大鼠发情，剂量高达 300 mg/kg。当 RU 486 在成年雌性大鼠中长期给药 15 天时，它没有表现出抗排卵活性；相反，它会引起血清 LH 和黄体酮水平以及卵巢重量的剂量依赖性增加。
RU 486 is an original multifaceted antihormone. It appears to be a potent progestin and glucocorticoid antagonist while exhibiting no agonistic effect, even at very high doses. Thus, according to the bioassay used, RU 486 administered orally at doses between 3 and 20 mg/kg completely inhibits the effect of exogenous progesterone on the endometrial proliferation in rabbits, on the volume density of uterine gland cell mitochondria, on the deciduomata formation and on the maintenance of pregnancy in ovariectomized rats. Furthermore, it proves to be antinidatory and abortive in rats and mice. In cycling monkeys it induces menstruation when administered during the mid-luteal phase.Acting as an antiglucocorticoid component, RU 486 effectively antagonizes, at 10M−6, dexamethasone’s effect on uridine incorporation into rat thymocytes RNA and on ACTH secretion from rat pituitary cells.In vivo(at a dose of 10 mg/kg to adrenalectomized rats) it fully prevents the thymolytic effect of corticosterone and dexamethasone; it also completely blocks urinary volume increase and potassium excretion induced by dexamethasone. In this latter test, its antiglucocorticoid activity is rapidly and fully reversed by increasing doses of dexamethasone. Using a perifusion technique, we observe that RU 486 does not inhibit corticosterone biosynthesis in rat adrenal cells stimulated by ACTH. The compound also possesses a moderate antiandrogenic activity on seminal vesicles and prostate weights, about 20 times weaker than its two other antagonist properties (evaluated in rats). In various species (rats, rabbits and mice) it exhibits a slight uterotrophic activity, approximately 10,000 times weaker than that of estradiol; but, unlike estrogens, it fails to induce estrus in ovariectomized rats given up to 300 mg/kg. When RU 486 is administered chronically for 15 days in adult female rats, it displays no antiovulatory activity; on the contrary, it provokes dose-dependent increases in serum LH and progesterone levels and ovarian weight.