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目的 从受体药理特性上分析米非司酮的抗生育作用及与糖皮质激素的作用。方法 应用放射配体结合检测技术 ,以3 H R5 0 2 0和3 H 地塞米松作为示踪物 ,采用饱和竞争性抑制分析方法 ,观察米非司酮与兔、猕猴子宫胞浆孕激素受体及大鼠肝脏糖皮质激素受体结合特性。结果 米非司酮可与兔、猕猴子宫胞浆孕激素受体牢固结合 ,很小剂量就可抑制3 H R5 0 2 0与孕激素受体结合。兔子宫孕激素受体结合实验所用米非司酮与孕酮的IC50 (5 0 %抑制浓度 )值分别为 6 6 1nmol/L、 2 6 2 0nmol/L ,差异有极显著性意义 (P <0 0 1) ,RBA (相对结合力 )为孕酮的 4 0倍 ;猕猴子宫胞浆孕激素受体结合实验中米非司酮与孕酮的IC50 值分别为 17 2 0、 30 2 0nmol/L ,差异有显著性意义 (P <0 0 5 ) ,其RBA为孕酮的 1 8倍。米非司酮可与大鼠肝脏胞浆糖皮质激素受体结合 ,较低浓度范围内就可抑制地塞米松与糖皮质激素受体结合 ,米非司酮、地塞米松的IC50 分别为 4 2 1、 14 5 0nmol/L ,RBA为地塞米松的 3 4倍。结论 对孕激素受体药理特性进行评估 ,米非司酮与孕激素受体有很强的亲和力 ,表现为较强的抗孕激素作用。以孕激素受体结合力为参照标准 ,显示米非司酮对孕激素受体结合力强度明显强于米非司酮对糖皮质激素受体结?
Objective To analyze the antifertility effect of mifepristone and the effect of glucocorticoids on its pharmacological properties. Methods Radioligand binding assay, 3 H R5 0 2 0 and 3 H dexamethasone as tracer, saturation competitive inhibition analysis was used to observe the relationship between mifepristone and rabbit, monkeys uterus progesterone Body and Rat Liver Glucocorticoid Receptor Binding Properties. Results Mifepristone could bind strongly to the progesterone receptor of the uterus of the rabbit and macaque uterus, and could inhibit the binding of the 3 H-R5 to the progesterone receptor at a very low dose. The IC50 (50% inhibition) of mifepristone and progesterone in rabbit uterus progesterone receptor binding experiment were respectively 6 6 1nmol / L and 2620nmol / L, the difference was extremely significant (P < 0 0 1), RBA (relative binding force) was 40 times that of progesterone; IC50 values of mifepristone and progesterone in the cytosolic progesterone receptor binding assay of rhesus monkeys were 1720 and 3020nmol / L, the difference was significant (P <0 05), the RBA was 18 times of progesterone. Mifepristone can bind to the hepatic cytoplasm glucocorticoid receptor in rats and inhibit the binding of dexamethasone and glucocorticoid receptor in the lower concentration range. The IC50 of mifepristone and dexamethasone are 4 211450nmol / L, RBA dexamethasone 34 times. Conclusion The pharmacological properties of progesterone receptor are evaluated. Mifepristone has strong affinity with progesterone receptor and exhibits strong antiprogestin effect. To progesterone receptor binding as a reference standard, showing that mifepristone progesterone receptor binding strength was significantly stronger than mifepristone glucocorticoid receptor node?