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.
Künig
G
G
Clinical Neurochemistry, Department of Psychiatry, University of Würzburg, Germany. kuenig@psi.ch
Niedermeyer
B
B
Deckert
J
J
Gsell
W
W
Ransmayr
G
G
Riederer
P
P
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