On the mode of action of a new contragestational agent (DL 111-IT)

• Published in: Contraception (Stoneham) Vol. 33; no. 3; pp. 263 - 283
• Main Authors: Galliani, G., Luzzani, F., Colombo, G., Conz, A., Mistrello, L., Barone, D., Lancini, G.C., Assandri, A.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.03.1986; Elsevier Science
• Subjects: Abortifacient Agents, Nonsteroidal; Animals; Biological and medical sciences; Birth control; Cricetinae; Decidua - anatomy & histology; Decidua - drug effects; DNA - biosynthesis; Female; Follicle Stimulating Hormone - blood; Glucosephosphate Dehydrogenase - metabolism; Gynecology. Andrology. Obstetrics; Lactates - metabolism; Lactic Acid; Luteinizing Hormone - blood; Medical sciences; Mesocricetus; Ornithine Decarboxylase - metabolism; Placenta - blood supply; Placenta - metabolism; Pregnancy; Prolactin - blood; Protein Biosynthesis; Rats; Rats, Inbred Strains; Receptors, Progesterone - metabolism; Regional Blood Flow - drug effects; RNA - biosynthesis; Triazoles - pharmacology; Uterus - blood supply; Uterus - metabolism; Trophoblaste; Induced abortion; Rodentia; Decidua; Pregnancy; Vertebrata; Mammalia; Placenta; Contragestive; Triazole derivatives; Early; Progesterone; Sex steroid hormone; Mechanism of action; Hormonal receptor
• ISSN: 0010-7824; 1879-0518
• DOI: 10.1016/0010-7824(86)90019-3

Non-hormonal compounds belonging to 3,5-diphenyl-1H,1,2,4 triazoles and chemically related classes (triazoles in short) are known to be endowed with high contragestational activity in rodents, dogs and primates. The data herein reported for one of the leaders of this family of compounds (DL 111-IT) along with those previously reported for some analogues, demonstrate that triazoles cause pregnancy arrest by a direct action on conception product. This action is expressed through a progressive slowing down of the conceptus development with a consequent onset of a state of anoxia, pregnancy arrest, degeneration of placentae and adnexae and their absorption or expulsion. The selective time of gestation during which they elicit the antifertility effect (early post-implantation period) and the histological examinations revealed that the target of their action are the ectoplacental and decidual cells. Biochemical studies on conceptus product demonstrate that, although they do not bind to progesterone receptors or inhibit ornithine decarboxy lase activity, triazoles induce an early and marked increase in the number of cytosol. progesterone receptors accompanied by a steep decrease in the ornithine decarboxylase activity in the product of conception. These findings are discussed in relatior to the possibility that triazoles may trigger pregnancy arrest by interfering with the chain of events by which progesterone regulates the mitotic activity of decidual and trophoblastic cells.