Prolonged antioestrogenic activity of ICI 46,474 in the ovariectomized mouse

Subcutaneous administration of ICI 46,474 (the trans isomer of 1 (p β dimethyl aminoethoxyphenyl) 1,2 diphonylbut 1 ene) (3 mg) to ovariectomized mice was found to produce vaginal refractoriness to subcutaneously administered oestradiol for up to 6 wk. Tritiated oestradiol 17 β accumulated in the uterus and vagina of the ovariectomized mouse, with maximum accumulation at 3 to 4 hr. This property of the target tissues was used to investigate the binding of tritiated oestradiol after the administration of 3 mg ICI 46,474 to ovariectomized mice. Radioactivity in the vagina was found to be comparable to control values 6 weeks after ICI 46,474 administration; uterine levels of radioactivity returned to control values by 10 wk. Administration of ICI 46,474 had an oestrogenic effect upon the mouse uterus whereas the vagina appeared to be initially stimulated and was then unable to respond to or to bind oestradiol.