Effects of seven clinically important antiepileptic drugs on inhibitory glycine receptor currents in hippocampal neurons

Kameel Karkar, Liu Lin Thio, Kelvin A. Yamada

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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 78±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.

Original languageEnglish (US)
Pages (from-to)27-35
Number of pages9
JournalEpilepsy Research
Volume58
Issue number1
DOIs
StatePublished - Jan 2004
Externally publishedYes

Fingerprint

Glycine Receptors
Anticonvulsants
Neurons
felbamate
Glycine
Carbamazepine
Valproic Acid
Phenytoin
Pentobarbital
Prosencephalon
Therapeutics

Keywords

  • Carbamazepine
  • Felbamate
  • Gabapentin
  • Pentobarbital
  • Phenytoin
  • Topiramate
  • Valproate

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Neurology

Cite this

Effects of seven clinically important antiepileptic drugs on inhibitory glycine receptor currents in hippocampal neurons. / Karkar, Kameel; Thio, Liu Lin; Yamada, Kelvin A.

In: Epilepsy Research, Vol. 58, No. 1, 01.2004, p. 27-35.

Research output: Contribution to journalArticle

Karkar, Kameel ; Thio, Liu Lin ; Yamada, Kelvin A. / Effects of seven clinically important antiepileptic drugs on inhibitory glycine receptor currents in hippocampal neurons. In: Epilepsy Research. 2004 ; Vol. 58, No. 1. pp. 27-35.
@article{96a4b3ffffe14fefa1793301382130c1,
title = "Effects of seven clinically important antiepileptic drugs on inhibitory glycine receptor currents in hippocampal neurons",
abstract = "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 78±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.",
keywords = "Carbamazepine, Felbamate, Gabapentin, Pentobarbital, Phenytoin, Topiramate, Valproate",
author = "Kameel Karkar and Thio, {Liu Lin} and Yamada, {Kelvin A.}",
year = "2004",
month = "1",
doi = "10.1016/j.eplepsyres.2003.12.002",
language = "English (US)",
volume = "58",
pages = "27--35",
journal = "Epilepsy Research",
issn = "0920-1211",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Effects of seven clinically important antiepileptic drugs on inhibitory glycine receptor currents in hippocampal neurons

AU - Karkar, Kameel

AU - Thio, Liu Lin

AU - Yamada, Kelvin A.

PY - 2004/1

Y1 - 2004/1

N2 - 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 78±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.

AB - 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 78±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.

KW - Carbamazepine

KW - Felbamate

KW - Gabapentin

KW - Pentobarbital

KW - Phenytoin

KW - Topiramate

KW - Valproate

UR - http://www.scopus.com/inward/record.url?scp=1842451462&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1842451462&partnerID=8YFLogxK

U2 - 10.1016/j.eplepsyres.2003.12.002

DO - 10.1016/j.eplepsyres.2003.12.002

M3 - Article

C2 - 15066672

AN - SCOPUS:1842451462

VL - 58

SP - 27

EP - 35

JO - Epilepsy Research

JF - Epilepsy Research

SN - 0920-1211

IS - 1

ER -