A new non-hormonal pregnancy-terminating agent.
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.
D000019:Abortifacient Agents / Q000494:pharmacology*; D000020:Abortifacient Agents, Nonsteroidal / Q000494:pharmacology*; D000315:Adrenalectomy; D000818:Animals; D002369:Castration; D006224:Cricetinae; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D007016:Hypophysectomy; D051379:Mice; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D011374:Progesterone / Q000097:blood; D051381:Rats; D014230:Triazoles / Q000494:pharmacology*
D000019:Abortifacient Agents; D000020:Abortifacient Agents, Nonsteroidal; D014230:Triazoles; D011374:Progesterone; C030266:3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1,2,4-triazole