Contraceptive and hormonal properties of a new 1,4-dihydro-2-oxoquinoline derivative (compound 84-182) in rodents and rhesus monkeys.
Compound 84-182 prevented pregnancy when administered subcutaneously at 10 mg/kg dose on days 3-8 post-coitum in hamsters and on days 6-10 post-coitum in guinea pigs. At lower doses, while in hamsters there was a marked reduction in implantation number, majority of implantations in guinea pigs showed signs of resorption. The compound was ineffective when administered at 10 mg/kg dose on days 1-3 or 6-7 post-coitum in hamsters and on days 1-5 or 4-8 post-coitum in rats. In rhesus monkeys, treatment with the compound at 5 and 10 mg/kg doses on days 16-21 of the menstrual cycle induced frank vaginal bleeding between days 21 and 24. Treatment on days 21-30 or after confirmation of pregnancy on days 32-36 was ineffective. In conventional bioassays, the compound was devoid of any estrogenic, antiestrogenic, progestational, antiprogestational, androgenic or antiandrogenic properties at the contraceptive dose. In competitive protein binding assay, the compound showed relative binding affinity (RBA) of less than 0.1% and 0.28% of progesterone, respectively, for rabbit and hamster uterine cytosol progesterone receptors. Its RBA for rat uterine cytosol estrogen receptors was less than 0.1% of estradiol-17 beta.
Singh
M M
MM
Division of Endocrinology, Central Drug Research Institute, Lucknow, India.
Mehrotra
P K
PK
Agnihotri
A
A
Srivastava
R P
RP
Seth
M
M
Bhaduri
A P
AP
Kamboj
V P
VP
D000818:Animals; D001667:Binding, Competitive; D003278:Contraceptives, Oral, Hormonal; D006224:Cricetinae; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D005260:Female; D008253:Macaca mulatta; D008297:Male; D008597:Menstrual Cycle / Q000187:drug effects; D008647:Mesocricetus; D011804:Quinolines / Q000494:pharmacology*; D015363:Quinolones; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D014599:Uterus / Q000187:drug effects / Q000378:metabolism
D003278:Contraceptives, Oral, Hormonal; D011804:Quinolines; D015363:Quinolones; C054673:3-cyano-3,4-dihydroquinoline-2(1H)-one; D004958:Estradiol