The purposes of this research are the investigation of the biochemical characteristics of developing central nervous system (CNS) cells in dispersed cell cultures, and the use of these cultures and sensitive biochemical tests to assess the toxicity, biochemical characteristics, and mechanisms of action of nervous system active drugs. We have used several in situ assay methods to provide evidence for a hierarchy of toxicity among anticonvulsants used to threat major motor seizures (Phenytoin is greater than Phenobarbital is greater than Carbamazepine) and among those drugs used to treat minor motor seizures (Valproic acid is greater than Diazepam is greater than Ethosuximide). Exposure of cultures to the minor motor anticonvulsants results in a selective depression of benzodiazepine (BOZ) receptor binding, and effect not observed with the major motor anticonvulsants. Studies of cortical and spinal cord cultures exposed chronically to diazepam reveal an apparent concentration related down regulation of the BDZ receptor. Cortical and spinal cultures show two specific BDZ receptor populations.
NIH ExPorter
NIH ExPorter