Maintenance of Pregnancy After Implantation in Hypophysectomized or Ovariectomized Mice Treated With Phenelzine Derivatives

Abstract

Some derivatives of phenelzine have been shown to interrupt pregnancy in mice, when given after implantation, i.e. on days 7\p=n-\10. Pregnancy can be maintained in mice treated with these compounds and in mice hypophysectomized on day 7 by administration of suspensions of whole mouse pituitaries, of human chorionic gonadotrophin or of progesterone given with a basic concentration of oestrogen. Prolactin was ineffective in maintaining pregnancy. The action of the phenelzine derivatives could also be reversed by 0\m=.\5\p=n-\ \g=m\g.luteinizing hormone and by 0\m=.\05 \g=m\g. oestradiol. The compounds antagonized the action of progesterone in maintaining pregnancy in ovariectomized mice and this indicates that they act on the uterus. There may be, in addition, a more central action, e.g. on the ovary or on the pituitary but this would be masked by the peripheral (i.e. uterine) effect.

The Maintenance of Pregnancy During the Pre-Implantation Period in Mice Treated With Phenelzine Derivatives

“…The action of WL 31 was not reversed by the LH, since none of the mice were pregnant at autopsy on day 11. This dose of LH has already been shown to reverse the effects of WL 31 given during days 7-10 (Jaitly et al 1968). Similarly 0-3 i.u.…”

“…In a previous paper we have shown that the phenelzine derivatives interrupt pregnancy in the post-implantation period by an action on the uterus resulting in an antagonism of the action of progesterone (Jaitly et al 1968). In the present study we have shown that during the pre-implantation period the compounds act on the pituitary or possibly on the hypothalamus.…”

“…The effect during the post-implantation period (i.e. days 7-10) was studied in greater detail (Jaitly, Sullivan, Robson & Wilson, 1968) and it was found that during this period these substances produced their effect by antagonizing the action of progesterone on the uterus. Progesterone, essential for the maintenance of pregnancy, was thus unable to exert its action.…”

“…CH2.CH,.NHNH, oestradiol, luteinizing hormone (NIH-LH-B3, bovine), prolactin, mouse pituitary suspension and HCG have been described previously (Jaitly et al 1968). Thirty phenelzine derivatives were investigated for their anti-fertility activity in mice, in the pre-implantation period; their structures are given in Table 1.…”