DL 111, a new non-hormonal antifertility agent: contragestational and kinetic profile in baboons

It was previously shown that 3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1,2,4 triazole (DL 111) given parenterally in single or multiple doses during the early stage of embryonal development terminates pregnancy in the mouse, the hamster, the rat, the rabbit and the dog. In the present work, the studies have been extended to the baboon. In this sub-human primate, single and/or multiple intramuscular injections of the compound terminated pregnancy when given between day 34 and 54 of gestation. The effectiveness of DL 111 was greater when earlier in gestation and the optimal mode of treatment appears to be a multiple one. DL 111 appears to act by a direct action on the conceptus, with consequent suppression of the endocrine function of the placenta, progesterone withdrawal and abortion. In all the baboons that aborted, the menstrual cycles resumed within a reasonable length of time and subsequent cycles were regular. All the animals that did not abort have given birth to normal and health term infants. Fertility appears to be unimpaired and the progeny resulting form these pregnancies did not show any abnormalities. No significant drug-related side-effects or alterations in plasma enzymes or haematological parameters were observed. Pharmacokinetic and activity relationships strongly suggest that sustained exposure of the conceptus to the drug action is indispensable for optimizing the pregnancy-terminating effect.