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Gallager DW, Mallorga P, Tallman JF. 
“Interaction Of Diphenylhydantoin And Benzodiazepines In The CNS”. 
Brain Research. 1980;189:209-220.
Using extracellular unit recording and microlontophoretic techniques, the anticonvulsant diphenylhydantoin (DPH) was found to increase the physiological efficacy of the benzodiazepines. This increased biological effect could be correlated with an enhanced specific binding of benzodiazopines measured in viva following pretreatment of rats with DPH. The increased binding of benzodiazepines is due to an increase in the total number of benzodiazepine binding sites without an alteration in the affinity of these sites for [3H]diazepam. The data show that the ejects of DPH on benzodiazepine binding are qualitatively different and independent from the effects of y-amino- butyric acid. Based on the dose-response relationship between benzodiazepine binding effects and the anticonvulsant activity of DPH and reports of other convulsant, anticonvulsant compounds which alter benzodiazepine binding, it is suggested that the benzodiazepine binding site may be relevant to convulsant-anticonvulsant activity.
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