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Modulation of specific [3H]phenytoin binding by benzodiazepines

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Abstract

We have shown that diazepam (ED50 2.4 μM), flunitrazepam (ED50 10.2 μM) and Ro5-4864 (ED50 5 μM) are able to enhance both total and specific [3H]phenytoin binding. Picrotoxin (IC50 1.43 μM) and chloride, either NaCl or KCl (IC50 42.4 μM) inhibit both the increase in total and specific binding of [3H]phenytoin, Ro 15-1788 does not. The optimum time for this enhancement was 3–4 hours. While the ED50's for the benzodiazepines are high their order of potency suggests that an involvement of both the “peripheral type” benzodiazepine receptor and the GABA-chloride ionophore complex is likely. Clonazepam (IC50 23 μM), oxazepam (IC50 12 μM) chlordiazepoxide (IC50 35 μM) and Ro8682-10, a convulsant benzodiazepine (IC50 16 μM) all inhibit both total and specific [3H]phenytoin binding. These effects were not blocked by chloride ions, picrotoxin or Ro 15-1788, and reached equilibrium within 45 minutes. This order of potency also parallels that for the ‘peripheral’ benzodiazepine receptor in rat brain. These data suggest the presence of a micromolar benzodiazepine receptor site which may play a role in the control of CNS excitability. Nitrazepam, medazepam, bromazepam and the tetralobenzodiazepines U38335, U42794, U43434, and U37834 had no effect on total or specific [3H]phenytoin binding nor on the actions of the other benzodiazepines described in concentrations up to 50 μM.

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  1. Department of Pharmacology, University of Toronto, M5S 1A8, Toronto, Ontario, Canada

    Lawrence Spero

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  1. Lawrence Spero
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Spero, L. Modulation of specific [3H]phenytoin binding by benzodiazepines. Neurochem Res 10, 755–765 (1985). https://doi.org/10.1007/BF00964533

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