Some endocrine effects of two phenothiazine derivatives, chlorpromazine and perphenazine, in the female mouse.

The effects of chlorpromazine and perphenazine were studied with both immature and mature female mice. At a dose of 5 mg/kg daily, each drug delayed the onset of sexual maturity in immature animals. In mature mice, a daily dose of 10 mg/kg inhibited vaginal oestrus and reduced the weights of the ovaries, vagina and uterus. Each of the two drugs inhibited ovarian hypertrophy following unilateral ovariectomy, but only slightly diminished the responses to exogenous oestrogen and to exogenous gonadotrophin. In one experiment, pseudopregnancy, as shown by a positive deciduoma-test, was provoked by perphenazine, but this experiment could not be repeated. Chlorpromazine failed to evoke a positive deciduoma response. At a dose of 10 mg/kg, neither drug caused a fall in levels of adrenal ascorbic acid. In the rat, treatment for 1 week with 10 mg/kg daily of either drug led to a rise in pituitary gonadotrophic activity. It was concluded that both drugs inhibited the release of gonadotrophins by the pituitary gland, independently of any action in releasing corticotrophin.