Inhibition of [3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid [AMPA] binding by the anticonvulsant valproate in clinically relevant concentrations: an autoradiographic investigation in human hippocampus.
The interaction of the anticonvulsant valproate with AMPA glutamate receptors in human post mortem hippocampus was investigated. At concentrations of > or = 100 microM valproate decreased binding of 40 nM [3H]AMPA to 45+/-56% of control level (CA 1). Clinically effective brain concentrations for valproate are estimated at 100-200 microM. Our results thus provide evidence that the anticonvulsant effects of valproate may partially be caused by interaction with AMPA receptors.
Clinical Neurochemistry, Department of Psychiatry, University of Würzburg, Germany. kuenig@psi.ch
G
G
Künig
B
B
Niedermeyer
J
J
Deckert
W
W
Gsell
G
G
Ransmayr
P
P
Riederer
D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000378:metabolism*; D001345:Autoradiography; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D014635:Valproic Acid / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism*
D000927:Anticonvulsants; D018690:Excitatory Amino Acid Agonists; D014635:Valproic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid