Effect of Anticonvulsant Drugs on (35S)t‐Butylbicyclophosphorothionate Bindingin Vitroandex Vivo

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Abstract
Using several concentrations of eight anticonvulsant drugs in clinical use (carbamazepine, clonazepam, phenytoin, phenobarbital, ethosuximide, primidone, sodium valproate, and D,L‐γ‐vinyl GABA), we studied their abilitiesin vitroto displace (35S)t‐butylbicyclophosphorothionate (35S‐TBPS) from its binding site in a homogenate of rat brain. Thereafter ethosuximide (150 mg/kg), phenobarbital (30 mg/kg), clonazepam (0.3 mg/kg), or phenytoin (100 mg/kg) was injected intraperitoneally into rats for 16–20 days; and the effect of drug administration on35S‐TBPS binding was studied in the cortex and hippocampusex vivo.Phenobarbital (100 μM, P35S‐TBPS bindingin vitroby 10–16%. After drug administration of phenobarbital (concentration in plasma 168 μM), the number of binding sites decreased and the binding affinity (P35S‐TBPS bindingin vitroat the concentration analogous to therapeutic plasma levels orex vivoat the dose used. These results suggest that the use of phenobarbital may modulate the TBPS binding site, but the role of the present findings in the anticonvulsant action of phenobarbital needs to be further studied.