CDRI-85/287: studies on competition to estrogen binding sites in the immature rat uterus.
Ability of compound CDRI-85/287, a new nonsteroidal antiestrogen with negligible inherent estrogenicity, to inhibit uptake of 3H-estradiol (3H-E2) by the immature rat uterus in vivo was investigated. Different doses of 85/287 were administered either intraperitoneally 30 min before 3H-E2 or orally 1 and 6 hr before 3H-E2. A dose dependent inhibition in 3H-E2 uptake was observed after administration of the compound by either route and was 69% at 50 micrograms/rat ip dose and 80% at 2.5 mg/kg po dose. In in vitro competitive binding assay, however, the compound showed poor affinity (RBA 0.42% of estradiol-17 beta) for cytosolic estrogen receptors. Considering the potent anti-estrogenic as well as anti-implantation efficacy of the compound, its action in vivo appears to be mediated via its active metabolite(s).
Sreenivasulu
S
S
Division of Endocrinology, Central Drug Research Institute, Lucknow, India.
Dwivedi
A
A
Singh
M M
MM
Setty
B S
BS
Kamboj
V P
VP
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D001665:Binding Sites; D001667:Binding, Competitive; D003600:Cytosol / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
D001578:Benzopyrans; D004965:Estrogen Antagonists; D010880:Piperidines; D011960:Receptors, Estrogen; C066624:CDRI 85-287; D004958:Estradiol