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A. P. LABHSETWAR and A. L. WALPOLE

Methallibure (ICI 33828) is a non-steroidal compound which has been found to inhibit secretion of gonadotrophins from the pituitary in a wide variety of species (Walpole, 1965). Decrease in pituitary gonadotrophin stores and/or secretion following treatment with methallibure has been found in the rat (Brown, 1963; W. R. Russell and A. L. Walpole, unpublished observations), pig (Garbers & First, 1969; Stormshak, Leverage, Kelley, Gerrits & Howland, 1970) and human (Loraine, Bell & Foss, 1965). The compound is also known to cause restriction of food intake with a consequent loss in body weight. It is not known whether a decrease in the gonadotrophin synthesis and/or release following the methallibure treatment stems from the specific effects of the compound or is secondary to a restriction of food intake. In the present communication, pituitary and serum lh

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M. J. K. HARPER and A. L. WALPOLE

Summary.

I.C.I. 46,474, the trans-isomer of 1-(p-β-dimethylaminoeth-oxyphenyl-1,2-diphenylbut-1-ene, is very effective in terminating early pregnancy by preventing implantation when given during the first 4 days after insemination to female rats. In this species, the compound is weakly and atypically oestrogenic and is also anti-oestrogenic, as indicated by its inhibitory effect on the response to exogenous oestrogens of the vaginal epithelium (cornification) and uterus (weight-increase). It is suggested that it can prevent implantation in rats by virtue of its anti-oestrogenic activity, i.e. by counteracting the oestrogen-release from the ovaries which is believed to occur on the 4th day and upon which implantation appears to depend.

The corresponding cis-isomer (I.C.I. 47,699) is very different in its properties and behaves in all respects like a conventional oestrogen (orally active—e.g. dienoestrol). In rats it is very much more potent as an oestrogen than I.C.I. 46,474—by which its uterotrophic action is inhibited. On the other hand the trans-isomer is the more potent of the two in inducing vaginal cornification in ovariectomized mice.