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.