Objetivo 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 BASES FOR IN VITRO TESTING ON CELL CULTURES OF THE TERATOGENESIS INDUCED BY ANTICONVULSIVANTS, INCLUDING NEURAL TUBE DEFECTS, CRANIOFACIAL ABNORMALITIES AND MENTAL RETARDATION. THIS WILL INVOLVE DESIGNING CELL TOXICITY, ANTI-MITOTIC, PRO-DIFFERENCIATIVE AND ADHESION ASSAYS. Ámbito científico natural sciencesbiological sciencesneurobiology Programa(s) FP1-BAP - Multiannual research action programme (EEC) in the field of biotechnology (BAP), 1985-1989 Tema(s) Data not available Convocatoria de propuestas Data not available Régimen de financiación CSC - Cost-sharing contracts Coordinador UNIVERSITY OF COPENHAGEN Aportación de la UE Sin datos Dirección NOERREGARDE 10 POSTBOKS 2117 KOEBENHAVN 1017 Dinamarca Ver en el mapa Coste total Sin datos Participantes (1) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo UNIVERSITY COLLEGE Irlanda Aportación de la UE Sin datos Dirección BLACKROCK CO. DUBLIN Ver en el mapa Coste total Sin datos
