INHIBITION OF PHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLE-PROPIONIC ACID[AMPA] BINDING BY THE ANTICONVULSANT VALPROATE IN CLINICALLY RELEVANTCONCENTRATIONS - AN AUTORADIOGRAPHIC INVESTIGATION IN HUMAN HIPPOCAMPUS

The interaction of the anticonvulsant valproate with AMPA glutamate re ceptors in human post mortem hippocampus was investigated. At concentr ations of greater than or equal to 100 mu M valproate decreased bindin g of 40 nM [H-3]AMPA to 45 +/- 56% of control level (CA 1). Clinically effective brain concentrations for valproate are estimated at 100-200 mu M. Our results thus provide evidence that the anticonvulsant effec ts of valproate may partially be caused by interaction with AMPA recep tors. (C) 1998 Elsevier Science B.V. All rights reserved.