Add time:09/24/2019         Source:sciencedirect.com

Azastene (4,4,17α-trimethylandrost-5-eno [2,3-d]isoxazol-17-ol), when given orally to rats at a dose of 12 mg/kg once on day 10 of pregnancy, induced resorption of all fetuses and a precipitous decline of circulating progesterone levels in all test animals. The disruption of pregnancy was prevented by a single, concurrent, subcutaneous injection of progesterone (4 mg/rat). Thus, the interruption of pregnancy occurs via an acute, short-term, reversible progesterone withdrawal. The reduction of progesterone levels is brought about by competitive inhibition of ovarian 3β-hydroxysteroid dehydrogenase activity. Despite its potency as an interceptive agent, azastene exhibited only moderate endocrine-related effects if given daily for 2 weeks to female rats at doses as high as 1000 mg/kg. Those effects were an increase in the number of vaginal estrous days and a dose-related increase in adrenal weight. The latter effect is consistent with the known adrenal inhibitory properties of this drug.

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