Yano S, Ikegami Y, Nakao K
Drug Discovery Research Unit, Ciba-Geigy Japan Ltd., Takarazuka, Japan.
Arzneimittelforschung. 1996 Feb;46(2):192-5.
The therapeutic effect of the new nonsteroidal aromatase inhibitor fadrozole hydrochloride (4-(5,6,7,8-tetrahydro-imidazo[1,5a]pyridin-5-yl)benzonitrile monohydrochloride, fadrozole, CAS 102676-31-3, CGS16949A) was assessed using a surgically induced endometriosis model in rats. In nontreated rats, the endometrial transplants on the abdominal wall developed large cysts with fluid. In the fadrozole treated group, the cystic volume of the transplants decreased in a dose-dependent manner. The weights of the hemi-uteri were markedly reduced by fadrozole treatment. Fadrozole produced a dose-dependent increase in percentage of vaginal diestrous days. In ovariectomized group, the growth of the transplants was also suppressed, and the weights of the hemi-uteri decreased markedly. Histologically, the signs of growth suppression and/or atrophic changes such as minimization of luminal size, cuboidal piknotic epithelium and/or contraction of stroma were observed in ovariectomized or fadrozole treated groups. The right uterine horns also showed marked atrophic changes as with the transplants. The present study strongly indicates that the new selective aromatase inhibitor fadrozole should be useful for the treatment of endometriosis.
使用手术诱导的大鼠子宫内膜异位症模型评估了新型非甾体芳香化酶抑制剂盐酸法倔唑（4-(5,6,7,8-四氢-咪唑并[1,5a]吡啶-5-基)苄腈盐酸盐，法倔唑，CAS 102676-31-3，CGS16949A）的治疗效果。在未治疗的大鼠中，腹壁上的子宫内膜移植物形成了充满液体的大囊肿。在法倔唑治疗组中，移植囊肿的体积呈剂量依赖性减小。法倔唑治疗可使半子宫重量显著降低。法倔唑使阴道动情后期天数的百分比呈剂量依赖性增加。在去卵巢组中，移植物的生长也受到抑制，半子宫重量显著下降。组织学上，在去卵巢或法倔唑治疗组中观察到生长抑制和/或萎缩变化的迹象，如管腔大小最小化、立方形固缩上皮和/或间质收缩。右侧子宫角也与移植物一样出现明显的萎缩变化。本研究有力地表明，新型选择性芳香化酶抑制剂法倔唑对子宫内膜异位症的治疗应是有效的。
