Pharmacological properties of a new selective antiprogestagen: Org 33628.
For antiprogestagens both selectivity (ratio of antiprogestational to antiglucocorticoid activity) and potency are important conditions for their applications in fertility regulation and correction of hormone-dependent irregularities. Org 33628 appears to fulfill both conditions most convincingly. The activities of this new antiprogestagen in various assays are compared with those of RU 38486 and a few other antiprogestagens. The binding of Org 33628 to the progesterone receptor is twice as high as that of RU 38486 whereas the binding to the glucocorticoid receptor is 25 times lower than that of RU 38486. The activity of Org 33628 in the pregnancy interruption test in rats is 16 times higher than that of RU 38486. The antiglucocorticoid activity of Org 33628 in rats is about eight times lower than that of RU 38486. In the ovulation inhibition test in rats Org 33628 is approximately 80 times more potent than RU 38486. For menses induction in the stumptail monkey activity observed for Org 33628 is only twice as high.


CONCLUSIONS
Org 33628 is a very potent and selective antiprogestagen with a remarkably high ovulation-inhibitory activity. The magnitude of the potency difference with RU 38486 is species and/or target organ dependent.
Kloosterboer
H J
HJ
Organon Scientific Development Group, Oss, The Netherlands.
Deckers
G H
GH
de Gooyer
M E
ME
Dijkema
R
R
Orlemans
E O
EO
Schoonen
W G
WG
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004963:Estrenes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005663:Furans / Q000494:pharmacology; D006067:Gonanes / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D015735:Mifepristone / Q000494:pharmacology; D010060:Ovulation / Q000187:drug effects; D011247:Pregnancy / Q000187:drug effects; D011372:Progestins / Q000037:antagonists & inhibitors*; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000378:metabolism; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship
D004963:Estrenes; D005663:Furans; D006067:Gonanes; D011372:Progestins; D011956:Receptors, Cell Surface; D011980:Receptors, Progesterone; C076196:Org 31710; C076197:Org 31806; D015735:Mifepristone; C094798:Org 33628; C053238:onapristone