Pregnancy interceptive efficacy and biological profile of 3-amino-6,7-dimethoxy-1H-pyrazolo [3,4-b] quinoline (compound 85/83) in rodents.
Administration of compound 85/83 during the peri- and post-implantation period intercepted pregnancy in hamster and guinea pig by parenteral route and in hamster by oral route also. The m.e.d. for hamster and guinea pig was 10 and 20 mg/kg, respectively; lower doses were less effective. Restricting the administration to early post-implantation schedule interrupted pregnancy partially in both species. The compound was, however, ineffective in rat and in the pre-implantation schedule (days 1-4 post-coitum) in hamster. When tested in vitro on growing trophoblasts at 13.8 x 10(-5) M concentration, it prevented growth and caused degeneration of the cells within 24 h; lower concentration (9.2 x 10(-5) M) was less effective. The compound was found to be devoid of estrogenic, antiestrogenic, progestational and antiprogestational properties in conventional bioassays. In hormone competition assays, its relative binding affinity (RBA) to estrogen receptor was negligible (0.002% of estradiol-17 beta), while for uterine cytosol progesterone receptors in rabbit and hamster was 0.06 and 0.08% of progesterone, respectively. The compound 85/83 appears to intercept pregnancy by interfering with development of trophoblast cells.
Division of Endocrinology, Central Drug Research Institute, Lucknow, India.
P K
PK
Mehrotra
R
R
Shukla
A
A
Dwivedi
R P
RP
Srivastava
N
N
Bhat
M
M
Seth
A P
AP
Bhaduri
V P
VP
Kamboj
D000284:Administration, Oral; D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D003270:Contraceptive Agents / Q000494:pharmacology*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D008297:Male; D009929:Organ Size; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D014327:Trophoblasts / Q000187:drug effects; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects; D014621:Vagina / Q000187:drug effects
D000634:Aminoquinolines; D003270:Contraceptive Agents; C071045:compound 85-83