PMID: 2109499Jan 1, 1990Paper

In vitro screening for anticonvulsant-induced teratogenesis in neural primary cultures and cell lines

International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience
C ReganD C Williams

Abstract

To establish inherent potential for the induction of neural tube defects the ability of selected anticonvulsant agents to interfere with cell division has been established in vitro using an antiproliferative assay in clonal cell lines and a cytotoxicity assay using primary cultures of cerebral cortex neurons at different stages of development. In order to evaluate the relative toxicities of these agents their in vitro effects were determined at 2-3 times the plasma therapeutic level. By these procedures valproate and the benzodiazepines, diazepam and clonazepam, exerted a potent antiproliferative action which could not be attributed to increased cytotoxicity. In contrast phenytoin was markedly cytotoxic but was without an antiproliferative action. This cytotoxicity was most pronounced during the periods of extensive fibre outgrowth. When compared to epidemiological and animal study data, agents which inhibited cell proliferation within twice therapeutic concentration were consistently associated with major neural tube malformations. However phenytoin, found to be positive in the cell cytotoxicity assay, is not associated with neural tube malformations but rather is primarily associated with mental retardation. Thus assessment o...Continue Reading

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Citations

Jul 25, 1998·Cell Motility and the Cytoskeleton·P S WalmodV Berezin
Jan 1, 1991·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·C Maguire, C M Regan
Jan 1, 1991·Toxicology in Vitro : an International Journal Published in Association with BIBRA·C M ReganD C Williams
Aug 1, 1995·Toxicology in Vitro : an International Journal Published in Association with BIBRA·B SchilterP Honegger
Sep 16, 1999·Biochemical Pharmacology·J NordenbergA Weizman
Feb 1, 1997·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·C Courage-MaguireC M Regan
Oct 1, 1996·Toxicology in Vitro : an International Journal Published in Association with BIBRA·V BerezinE Bock
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May 25, 2002·Food Additives and Contaminants·J Perkowski, T Basiński
Jul 26, 2003·Food Additives and Contaminants·J PerkowskiT Basiński
Oct 1, 1995·Experimental Dermatology·M ArtucD Schadendorf

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