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Teratogenic effect of AY 9944 in rats: importance of the day of administration and maternal plasma cholesterol level.

Abstract
An inhibitor of cholesterol synthesis, AY 9944 (trans-1,4-bis(2-chlorobenzylaminomethyl) cyclohexane dihydrochloride) is teratogenic. A single dose of AY 9944 (50 mg/kg or 75 mg/kg) given to Wistar pregnant rats on the second, fourth, sixth, seventh, or eighth day of gestation induced malformations such as holoprosencephaly. They were often limited to isolated pituitary agenesis. The highest percentage of holoprosencephalic fetuses was found when AY 9944 was given on the fourth day of gestation. Whatever the dose and the day of administration, the lower the maternal plasma cholesterol level, the more frequent were holoprosencephalic fetuses. Therefore, it is suggested that the decrease in maternal plasma cholesterol level is at least one of the factors provoking holoprosencephaly.
AuthorsV Barbu, C Roux, R Dupuis, J Gardette, J C Maziere
JournalProceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.) (Proc Soc Exp Biol Med) Vol. 176 Issue 1 Pg. 54-9 (May 1984) ISSN: 0037-9727 [Print] United States
PMID6200888 (Publication Type: Journal Article)
Chemical References
  • Cyclohexanes
  • Teratogens
  • trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride
  • Cholesterol
Topics
  • Abnormalities, Drug-Induced (etiology)
  • Animals
  • Cholesterol (blood)
  • Cyclohexanes (adverse effects)
  • Female
  • Fetal Death (chemically induced)
  • Gestational Age
  • Head (abnormalities)
  • Pregnancy
  • Rats
  • Rats, Inbred Strains
  • Teratogens (pharmacology)
  • trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride (adverse effects)

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