Effects of seven clinically important antiepileptic drugs on inhibitory glycine receptor currents in hippocampal neurons.
Although potentiation of the inhibitory glycine receptor (GlyR) may contribute to the mechanism of action of antiepileptic drugs (AEDs), the effects of AEDs on GlyRs have not been investigated in detail in forebrain neurons. We examined the effects of seven clinically important AEDs on GlyR-mediated currents using whole-cell patch clamp recordings from cultured embryonic mouse hippocampal neurons. At high therapeutic concentrations, topiramate (in 24% of neurons) and pentobarbital reversibly decreased glycine currents to 89+/-6 % and 81+/-7 % of control, respectively. At or below therapeutic concentrations, carbamazepine, felbamate, gabapentin, phenytoin, and valproate had no effect on glycine currents, while at supratherapeutic concentrations these agents produced modest reversible inhibition. We conclude that GlyR potentiation does not contribute to the antiepileptic action of the seven AEDs examined.
Karkar
Kameel M
KM
Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Thio
Liu Lin
LL
Yamada
Kelvin A
KA
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005998:Glycine / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques / Q000379:methods; D018009:Receptors, Glycine / Q000187:drug effects* / Q000502:physiology
D000927:Anticonvulsants; D002712:Chlorides; D018009:Receptors, Glycine; D005998:Glycine