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A new non-hormonal pregnancy-terminating agent

, : A new non-hormonal pregnancy-terminating agent. Contraception 23(2): 163-180

DL 111-IT, 3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1,2,4 triazole, a compound belonging to a new class of non-hormonal antifertility agents, when given subcutaneously, intramuscularly, intravaginally or orally terminates pregnancy in the rat, the mouse, the hamster and the dog. Time-course and dose-activity studies indicate that its effectiveness is dependent on dose, vehicle, route and time of pregnancy. DL 111-IT has no pre-implantation activity. The most effective time for treatment is the early post-implantation period. The compound has an antifertility effect through a slow and continuing action that results in the degeneration and subsequent resorption or expulsion of conceptuses. As a result, there must be sustained availability of active principle to arrest the pregnancy. Administered parenterally in a proper vehicle (oily) and with a suitable schedule of treatment (x 2-5 days), it demonstrates a very high pregnancy terminating activity (ED50: 0.04-0.7 mg/kg/day). Multiple intravaginal and oral administrations are also effective but the daily doses required are 10-20 and 40-100 times higher than the parenteral ones. Studies of the mechanism of action indicate that the site of action is the utero-placental complex. In fact, in pregnant rats, mice, hamsters and dogs, both plasma progesterone levels and the ineffectiveness of progesterone therapy rule out luteolysis as a basis for the activity. Moreover in hypophysectomized, ovariectomized animals whose pregnancies were maintained with proper hormonal treatments, DL 111-IT terminates pregnancy and adrenalectomy does not prevent its effect, which suggests that pituitary, ovaries and adrenals are not required for the antifertility action.


PMID: 7238042

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