Details

Autor(en) / Beteiligte

• Schilter, B.
• Nöldner, M.
• Chatterjee, S.s.
• Honegger, P.

Titel

Anticonvulsant drug toxicity in rat brain cell aggregate cultures

Ist Teil von

• Toxicology in vitro, 1995-08, Vol.9 (4), p.381-386

Ort / Verlag

Oxford: Elsevier Ltd

Erscheinungsjahr

1995

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• As an extension of a previous validation study, the concentration-dependent effects of a series of anticonvulsant drugs were examined in aggregating cell cultures of foetal rat telencephalon. Cultures were treated either at an early (day 5 to day 14) or at an advanced (day 20 to day 28) developmental stage, and assayed for changes in the activities of the cell type-specific enzymes choline acetyltransferase (ChAT), acetylcholinesterase (AChE), glutamic acid decarboxylase (GAD), glutamine synthetase (GS) and 2′,3′-cyclic nucleotide 3′-phosphohydrolase (CNP). Five drugs (carbamazepine, diazepam, phenobarbital, phenytoin and valproate), currently used in the treatment of epileptic patients, were tested together with losigamone, a recently developed anticonvulsant. The results show distinct, concentration-dependent patterns of biochemical changes for the different drugs. Phenytoin, carbamazepine, losigamone and diazepam greatly reduced GAD, ChAT and AChE activities, indicating a relatively high neuron-specific toxic potential. Diazepam produced a more general pattern of toxicity and, in contrast to the anticonvulsants, showed higher toxicity in less-differentiated cultures. Phenobarbital and valproate slightly but significantly increased the activities of several enzymes. The patterns of concentration-dependent effects observed in this three-dimensional cell culture system are in good agreement with the presumed neurotoxic and/or teratogenic potential of these drugs.