European Commission logo
español español
CORDIS - Resultados de investigaciones de la UE
CORDIS
Contenido archivado el 2024-04-15

IN VITRO SCREENING FOR ANTICONVULSANT TERATOGENESIS IN NEURAL PRIMARY CULTURES AND CELL LINES

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 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.

Tema(s)

Data not available

Convocatoria de propuestas

Data not available

Régimen de financiación

CSC - Cost-sharing contracts

Coordinador

UNIVERSITY COLLEGE DUBLIN
Aportación de la UE
Sin datos
Dirección
FOSTER AVENUE
BLACKROCK
Irlanda

Ver en el mapa

Coste total
Sin datos

Participantes (1)