Obiettivo VALIDATION OF NEW IN VITRO TESTS FOR THE PREVISION OF NERVOUS SYSTEM TERATOGENESIS BY DRUGS. The teratogenic potential of pharmaceutical agents was evaluated in vitro using an antiproliferative assay in clonal cell lines and a cytotoxicity assay employing primary cultures of cerebral cortex neurons at different stages of their development. Anticonvulsant agents with an ability to induce neural tube defects in vivo, valproate and the benzodiazepines (diazepam and clonazepam), were shown to have an antiproliferative action in neuroblastoma and glioma cell lines at 2-3 times their therapeutic serum concentrations and this was not due to cytotoxic action. Agents with a cytoxic action (phenytoin and some barbiturates) could be associated with their known in vivo impairment of neurodevelopment. Nonteratogenic analogues of valproate had no antiproliferative effect in clonal cell lines and the cytotoxic effect of certain barbiturates on primary cortical neurons had a specific structure activity requirement. In vivo systems evaluating induction of early differentiation markers and change in adhesiveness had poor discriminatory potential. The convulsive agent lindane was shown to inhibit picrotoxin binding and to facilitate transmitter release in vitro.ESTABLISH THE BASIS FOR IN VITRO TESTING ON CELL CULTURES OF THE TERATOGENESIS INDUCED BY ANTICONVULSANTS, INCLUDING NEURAL TUBE DEFECTS, CRANIOFACIAL ABNORMALITIES AND MENTAL RETARDATION. THIS WILL INVOLVE DESIGNING CELL TOXICITY, ANTI-MITOTIC, PRO-DIFFERENTIATIVE AND ADHESION ASSAYS. Campo scientifico natural sciencesbiological sciencesneurobiology Programma(i) FP1-BAP - Multiannual research action programme (EEC) in the field of biotechnology (BAP), 1985-1989 Argomento(i) Data not available Invito a presentare proposte Data not available Meccanismo di finanziamento CSC - Cost-sharing contracts Coordinatore UNIVERSITY COLLEGE DUBLIN Contributo UE Nessun dato Indirizzo FOSTER AVENUE BLACKROCK Irlanda Mostra sulla mappa Costo totale Nessun dato Partecipanti (1) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto UNIVERSITY OF COPENHAGEN Danimarca Contributo UE Nessun dato Indirizzo COPENHAGEN Mostra sulla mappa Costo totale Nessun dato