Killinger J, Hahn D W, Phillips A, Hetyei N S, McGuire J L
Contraception. 1985 Sep;32(3):311-9. doi: 10.1016/0010-7824(85)90054-x.
Norgestimate is a new orally active progestational agent. Studies were conducted to demonstrate that norgestimate is active pharmacologically without requiring biotransformation to an active metabolite. In in vitro studies, norgestimate exhibited a relatively high affinity for the rabbit uterine progestogen receptor. To demonstrate that norgestimate was not being degraded to a biologically active entity, which was binding to receptor sites in the cytosol preparation, the stability of 14C-norgestimate in the preparation was determined. Following the incubation of 14C-norgestimate with the cytosol fraction used in the receptor assay, the labeled material was extracted and analyzed by reverse phase high performance liquid chromatography. 14C-Norgestimate was recovered from these incubation mixtures, confirming that norgestimate was available to bind to the progestogen receptor. In in vivo studies, norgestimate stimulated the endometrium in immature rabbits when applied directly to the uterus, again suggesting that bio-transformation to an active metabolite is not required for expression of norgestimate's pharmacological activity. These in vitro and in vivo studies, when considered with previously reported studies, show that norgestimate is a unique progestogen.
诺孕酯是一种新型口服活性孕激素。已开展研究以证明诺孕酯具有药理活性，无需生物转化为活性代谢物。在体外研究中，诺孕酯对兔子宫孕激素受体表现出相对较高的亲和力。为证明诺孕酯不会降解为与胞质溶胶制剂中的受体位点结合的生物活性实体，测定了制剂中14C-诺孕酯的稳定性。将14C-诺孕酯与受体测定中使用的胞质溶胶部分一起孵育后，提取标记物质并通过反相高效液相色谱进行分析。从这些孵育混合物中回收了14C-诺孕酯，证实诺孕酯可与孕激素受体结合。在体内研究中，当直接应用于未成熟兔子宫时，诺孕酯可刺激子宫内膜，这再次表明诺孕酯药理活性的表达不需要生物转化为活性代谢物。这些体外和体内研究与先前报道的研究一起考虑时，表明诺孕酯是一种独特的孕激素。
