Differential effects of anticonvulsants on developing neurons in vitro

The effects of four anticonvulsants, phenobarbital, diphenylhydantoin (DPH), carbamazepine and valproic acid, on dissociated cultures of embryonic chick dorsal root ganglia (DRG) neurons were examined. DPH and valproic acid inhibited process formation in a dose-dependent manner and reduced neuronal production of substrate attached neurite promoting activity (SANPA). Less inhibition of process formation occurred with phenobarbital and carbamazepine and these two anticonvulsants had no effect on SANPA production. Substrate attachment of neurons, their survival and receptor interactions of DRG neurons with nerve growth factor were not influenced by any of the four anticonvulsants. These data suggest a rank ordering of direct toxic effects of anticonvulsants on developing neurons. The mechanisms of this neurotoxicity may include decreased neuronal production of autostimulating neurite promoting factors.