Phenytoin, an antiepileptic drug, competitively blocked non-NMDA receptors produced by Xenopus oocytes.
The blocking effect of phenytoin (PHT) and other antiepileptic agents on the glutamate receptors was investigated under voltage-clamp conditions using Xenopus oocytes that translated ddY-stock mouse brain mRNA. PHT shifted the concentration-response curve for kainate to right without significant block on the maximum response obtained, indicating that PHT competitively blocks the non-NMDA receptors. An apparent dissociation constant of PHT was 1.9 x 10(-4) M. The block was voltage-independent. Other antiepileptic agents examined hardly blocked the kainate responses except phenobarbital that blocked the responses. The possibility that the competitive block constitutes a part of the antiepileptic action of PHT was discussed.
Kawano
H
H
Department of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Sashihara
S
S
Mita
T
T
Ohno
K
K
Kawamura
M
M
Yoshii
K
K
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism*; D010672:Phenytoin / Q000494:pharmacology*; D011061:Poly A / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D014981:Xenopus
D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists; D012333:RNA, Messenger; D017470:Receptors, Glutamate; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D011061:Poly A; D010672:Phenytoin; D007608:Kainic Acid